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catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site
catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site
concerted reaction of dRP lyase and DNA polymerization of Li Polbeta on a uracil-containing DNA participating in single-nucleotide base excision repair (BER), beta-elimination reaction
catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site
DNA polymerase beta (Pol beta) catalyzes both DNA synthesis at the 3'-hydroxyl terminus and esxcision of 5'-dRP moiety prior to completion of the base excsion repair (BER) by DNA ligase
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catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site
DNA polymerase beta as the major polymerase involved in repair of oxidative base lesions, in single nucleotide replacement mechanisms. The 5'-deoxyribosephosphate lyase activity of Pol beta is essential for repair
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catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site
enzyme cleaves 3' to apurinic/apyrimidinic sites and is capable of removing 5' dRP residues at sites that mimic preincision with AP endonuclease. The activity of UL30 on the preincised and nicked substrates ist significantly greater than observed on apurinic/apyrimidinic DNA. These activities are integral to base excision repair and lead to DNA cleavage on 3' side on abasic sites and 5'-dRP residues that remain after cleavage by 5'-AP endonuclease, via beta-elimination forming a Schiff base intermediate
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catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site
enzyme is involved in single-nucleotide base excision DNA repair, SN-BER
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catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site
homologous to the dRP lyase activity of polymerase beta, pol beta. Proposed to participate in single-nucleotide base excision repair in mammalian cells, which is the major repair pathway in eukaryotic cells responsible for repair of lesions that give rise to abasic siles in DNA
catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site
in reactions reconstituted with uracil-DNA glycosylase, apurinic/apyrimidinic endonuclease and ligase I, pol iota can use its dRP lyase and polymerase activities to repair G-U and A-U pairs in DNA, a specialized form of base excision repair, BER. pol iota has an intrinsic dRP lyase activity and the reactions proceeds via beta-elimination involving an active residue containing a primary amine
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catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site
NEIL1 and NEIL2 are capable of removing 2-deoxyribose 5-phosphate from DNA with the effiency comparable to that of Polbeta, and they can substitute for Polbeta dRPase activity in a reconstituted base excision repair (BER) system
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catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site
reaction is part of the DNA base excision repair BER, enzyme releases 5'-terminal deoxyribose phosphate from preincised apurinic/apyrimidinic site DNA by beta-elimination
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catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site
removal of the 5'-deoxyribose phosphate group is a pivotal step in the base excision repair (BER) pathway in vivo.Two important enzymatic steps in mammalian single-nucleotide base excision repair are contributed by beta-pol: DNA resynthesis of the repair patch und lyase removal of 5'-deoxyribose phosphate
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catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site
TcPolbeta and TcPolbetaPAK, homologous to mammalian DNA polymerasebeta both show dRP lyase activity. The efficiency is not as high as the human Polbeta enzyme
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catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site
the catalytic subunit of pol gamma catalyzes the release of the the 5'-deoxyribose phosphate residue from incised apurinic/apyrimidinic sites to produce a substrate for DNA ligase. The ability to trap covalent enzyme DNA complexes with NaBH4 implicates Schiff base intermediate in an beta-elimination reaction mechanism
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catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site
the mitochondrial DNA polymerase in the parasite Crithidia fasciculata exhibits dRP lyase but shows deficiency in the release of dRP from the enzyme following its cleavage from the DNA
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catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site
Trf4 is able to form a Schiff base intermediate with a 5'-deoxyribose-5-phosphate substrate and to excise the abasic residue throuigh a dRP lyase activity and plays a role in single-nucleotide pathway of the base excision repair system. The dRP lyase reaction proceeds through a beta-elimination mechanism, verified by the addition of NaBH4 to trap the Schiff base intermediate, forming a covalent enzyme-DNA complex
catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site
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-
-
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25-mer-deoxyoligonucleotide 3'-labeled uracil-containing DNA duplex
? + 2-deoxy-D-ribose 5-phosphate
-
[32P]-labeled substarte, treated with uracil-DNA glycosylase and apurinic/apyrimidinic endonuclease
the products are stabilized by NaBH4 reduction of the Schiff base, formed between the catalytic nucleophile of the dRP lyase and C1' of rhe 2-deoxyribose 5-phosphate site, verifying the dRP removal by a beta-elimination
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?
28-mer deoxyoligonucleotide with a 5' uracil residue
?
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pretreated with Eschericia coli uracil N-glycosylase
-
-
?
34-bp oligonucleotide containing uracil at position 16
? + 2-deoxy-D-ribose 5-phosphate
labelled with 3'-end by terminal deoxynucleotidyltransferase using [alpha-32P]ddATP and annealed to its complementary oligonucleotide, and pretreated with human uracil-DNA glycosylase and AP endonuclease
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-
?
34-bp-deoxyoligonucleotide duplex containing a uracil residue at position 16
? + 2-deoxy-D-ribose phosphate
-
preincised [32P] apurinic/apyrimidinic site containing DNA, pretreated with uracil DNA-glycosylase and AP endonuclease
the reaction products are separarted by electrophoresis
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?
34-bp-oligonucleotide containing uracil at position 16
19-bp-oligonucleotide + 2-deoxy-D-ribose 5-phosphate
labelled with 3'-end by terminal deoxynucleotidyltransferase using [alpha-32P]ddATP and annealed to its complementary oligonucleotide, and pretreated with human uracil-DNA glycosylase and AP endonuclease
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-
?
34-mer-deoxyoligonucleotide containing a uracil residue at position 16
18-mer-deoxyoligonucleotide + 2-deoxy-D-ribose 5-phosphate
-
pretreated with uracil-N-glycosylase and apurunic/apyrimidinic endonuclease
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-
?
35-bp-deoxyoligonucleotide duplex containing a uracil residue at position 15
? + 2-deoxy-D-ribose phosphate
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in vitro single-nucleotide base excision DNA repair assay, containing amongst others uracil DNA-glycosylase, AP endonuclease and ligase I
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-
?
49-bp oligodeoxynucleotide containing uracil at position 21
? + 2-deoxy-D-ribose 5-phosphate
-
labelled at 3'-end with [alpha-32P]ddATP by terminal deoxynucleotidyl transferase and annealed to an unlabelled complementary strand containing a G residue opposite the uracil. Before use, the substrate is treated with uracil-DNA glycosylase and AP endonuclease to generate a single nucleotide gap directly upstream from the labelled fragment containing a deoxyribose phosphate flap
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-
?
49-residue oligonucleotide duplex DNA
? + 2-deoxy-D-ribose 5-phosphate
substrate contains uracil residue at position 21. The DNA is pretreated with uracil DNA glycosylase and AP endonuclease
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-
?
5'-deoxyribose phosphate DNA substrate
?
-
-
-
?
50-bp DNA containing a single abasic site preincised with AP endonuclease
29-bp DNA fragment + 2-deoxy-D-ribose 5-phosphate
-
-
-
-
?
52-pb synthetic duplex DNA
? + 2-deoxy-D-ribose 5-phosphate
labelled [32P]-uracil at position 22, pretreated with uracil DNA-glycosylase and Escherichia coli endonuclease IV
the percentage of total 2-deoxyribose 5-phosphate excised is calculated by dividing the amount of the dRP lyase product formed in each reaction by the sum of this product and the amount of the substrate DNA containing intact 5'-deoxyribose-5-phosphate
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?
closed-circular double-stranded DNA substrate bearing a single 8-oxoguanine/cytosine base pair at a defined position
? + 2-deoxy-D-ribose 5-phosphate
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-
-
-
?
closed-circular double-stranded DNA substrate bearing a single dihydrouracil/guanine base pair at a defined position
? + 2-deoxy-D-ribose 5-phosphate
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-
-
-
?
DNA with a 5'-incised apurinic/apyrimidinic site at position 21
? + 2-deoxy-D-ribose 5-phosphate
-
the uracil-DNA glycosylase-reacted DNA substrate is treated with AP endonuclease in the presence of MgCl2 to create a substrate containing a 5'-incised apurinic/apyrimidinic site. The resulting DNA substrate with a deoxyribose phosphate moiety at the 5'-end and a phosphate at the 3'-terminus is incubated with beta-pol or its amino-terminal 8-kDa domain
beta-pol is proposed to catalyze the release of the 5'-deoxyribose phosphate moiety from the cleaved apurinic/apyrimidinic site via a beta-elimination mechanism, producing 4-hydroxy-2-pentenal-5-phosphate
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?
labeled uracil-containing DNA
? + 2-deoxy-D-ribose 5-phosphate
[32P]-labeled, treated with with uracil-DNA glycosylase and apurinic/apyrimidinic endonuclease
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-
?
mimic of a preincised DNA duplex with a 5'dRP at the site of the nick
14-mer-oligonucleotide + 2-deoxy-D-ribose 5-phosphate
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nick substrate, containing a 3'-[32P]-labelled 16-mer with a terminal 5'-uracil, which upon pretreatment with uracil-DNA glycosylase is converted to an oligonuceotide with a 5' dRP residue, having a electrophoretic mobility of a 14.5-mer
removal of 5'dRP generates a 3'-[32P]-labelled 14-mer
-
?
preincised apurinic/apyrimidinic DNA
?
-
-
-
-
?
preincised DNA duplex with a 5'dRP flap
15-mer-oligonucleotide + 2-deoxy-D-ribose 5-phosphate
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flap substrate, containing a 3'-[32P]-labelled 16-mer that possesses a 5' uracil flap, which upon pretreatment with uracil-DNA glycosylase is converted to an oligonuceotide with a 5' dRP flap, having a electrophoretic mobility of a 15.5-mer
the removal of the 5' dRP generates a 3'-[32P]-labelled 15-mer
-
?
additional information
?
-
additional information
?
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catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site. According to the lyase catalytic mechanism, the epsilon-amino group of a catalytic lysine reacts with C1'-carbon of an AP site producing a Schiff base intermediate
-
-
?
additional information
?
-
catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site. According to the lyase catalytic mechanism, the epsilon-amino group of a catalytic lysine reacts with C1'-carbon of an AP site producing a Schiff base intermediate
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-
?
additional information
?
-
-
catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site. According to the lyase catalytic mechanism, the epsilon-amino group of a catalytic lysine reacts with C1'-carbon of an AP site producing a Schiff base intermediate
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-
?
additional information
?
-
5'-deoxyribose phosphate (5'-dRP)-processed DNA substrate, the processed dsDNA substrate consists of one nucleotide gap and a 5'-dRP group, synthesis overview. 5'-RP lyase activity is dependent on unique plant organellar DNAP insertions
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-
?
additional information
?
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5'-deoxyribose phosphate (5'-dRP)-processed DNA substrate, the processed dsDNA substrate consists of one nucleotide gap and a 5'-dRP group, synthesis overview. 5'-RP lyase activity is dependent on unique plant organellar DNAP insertions
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-
?
additional information
?
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-
5'-deoxyribose phosphate (5'-dRP)-processed DNA substrate, the processed dsDNA substrate consists of one nucleotide gap and a 5'-dRP group, synthesis overview. 5'-RP lyase activity is dependent on unique plant organellar DNAP insertions
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-
?
additional information
?
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-
reaction is part of the DNA base excision repair BER
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-
?
additional information
?
-
in addition to removal of 5'-deoxyribose phosphate from base excision repair intermediates, enzyme also removes 5'-adenylated deoxyribose phosphate from base excision repair intermediates after abortive ligation
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-
?
additional information
?
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catalysis of the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site in DNA where a DNA-(apurinic or apyrimidinic site) lyase has already cleaved the C-O-P bond 3' to the apurinic or apyrimidinic site. The reaction mechanism of the lyase reaction involves a transient covalent enzyme-DNA intermediate in the form of a Schiff base connecting Lys72 of the enzyme with the 5'-dRP moiety. The Schiff base intermediate is resolved via a beta-elimination reaction, initiated by abstraction of a C2'-H atom from the 5'-deoxyribose phosphate (5'-dRP) moiety
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-
?
additional information
?
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-
no reaction with a DNA substrate possessing 5' uracil flap
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-
?
additional information
?
-
the dRP removal proceeds through a beta-elimination, verified by addition of sodium borohydride forming a covalent protein-DNA complex by reduction of the Schiff base intermediate
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-
?
additional information
?
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-
the dRP removal proceeds through a beta-elimination, verified by addition of sodium borohydride forming a covalent protein-DNA complex by reduction of the Schiff base intermediate
-
-
?
additional information
?
-
-
removal of the 5'-deoxyribose phosphate group is a pivotal step in the base excision repair (BER) pathway in vivo
-
-
?
additional information
?
-
-
dRP lyase activity of the C-terminal domain of Rev1. Preparation of the 3'-end labeled dRP lyase substrate: 32P-labeled duplex DNA is pretreated with UDG and APE1 to prepare the single-nucleotide gapped substrates that contain 5'-dRP (5'-deoxyribose phosphate) flap and a 3'-OH at the margins, the S-S bond is included in the substrate molecule, overview. In vitro base excision repair (BER) activity. For kinetic analysis, a 34-bp duplex DNA substrate is prepared by annealing three DNA strands. The substrate contains an 18mer DNA strand with 6-FAM at the 3'-end and 5'-RP flap at the margin of a single-nucleotide gap
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-
?
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Aberrant Crypt Foci
Folate deficiency provides protection against colon carcinogenesis in DNA polymerase {beta} haploinsufficient mice.
Adenocarcinoma
DNA polymerase beta expression differences in selected human tumors and cell lines.
Adenoma
Genetic variation in the base excision repair pathway, environmental risk factors, and colorectal adenoma risk.
Adenoma
Inherited predisposition to colorectal adenomas caused by multiple rare alleles of MUTYH but not OGG1, NUDT1, NTH1 or NEIL 1, 2 or 3.
Adenoma
Rapid recognition of aberrant dHPLC elution profiles using the Transgenomic Navigator software.
Brain Neoplasms
Elevated expression of DNA polymerase beta gene in glioma cell lines with acquired resistance to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3- nitrosourea.
Breast Neoplasms
Comprehensive Profiling of DNA Repair Defects in Breast Cancer Identifies a Novel Class of Endocrine Therapy Resistance Drivers.
Breast Neoplasms
DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
Breast Neoplasms
Genetic variations in 3'UTRs of SMUG1 and NEIL2 genes modulate breast cancer risk, survival and therapy response.
Breast Neoplasms
PEG-functionalized zinc oxide nanoparticles induce apoptosis in breast cancer cells through reactive oxygen species-dependent impairment of DNA damage repair enzyme NEIL2.
Breast Neoplasms
Perturbation of base excision repair sensitizes breast cancer cells to APOBEC3 deaminase-mediated mutations.
Burkitt Lymphoma
Detection of genomic aberrations in molecularly defined Burkitt lymphoma by array-based high resolution single nucleotide polymorphism analysis.
Carcinogenesis
Cervical carcinoma risk associate with genetic polymorphisms of NEIL2 gene in Chinese population and its significance as predictive biomarker.
Carcinogenesis
DNA polymerase beta expression differences in selected human tumors and cell lines.
Carcinogenesis
Folate deficiency provides protection against colon carcinogenesis in DNA polymerase {beta} haploinsufficient mice.
Carcinogenesis
Functional variants of the NEIL1 and NEIL2 genes and risk and progression of squamous cell carcinoma of the oral cavity and oropharynx.
Carcinoma
Cervical carcinoma risk associate with genetic polymorphisms of NEIL2 gene in Chinese population and its significance as predictive biomarker.
Carcinoma
Functional variants of the NEIL1 and NEIL2 genes and risk and progression of squamous cell carcinoma of the oral cavity and oropharynx.
Carcinoma
Overexpression of DNA polymerase iota (Pol?) in esophageal squamous cell carcinoma.
Carcinoma, Hepatocellular
Hepatitis C virus induces oxidative stress, DNA damage and modulates the DNA repair enzyme NEIL1.
Carcinoma, Hepatocellular
Polymorphisms of base-excision repair genes and the hepatocarcinogenesis.
Carcinoma, Squamous Cell
Functional variants of the NEIL1 and NEIL2 genes and risk and progression of squamous cell carcinoma of the oral cavity and oropharynx.
Cataract
A variant in a microRNA binding site in NEIL2 3'UTR confers susceptibility to age-related cataracts.
Cataract
Regulated over-expression of DNA polymerase beta mediates early onset cataract in mice.
Cockayne Syndrome
Cockayne Syndrome group B protein stimulates NEIL2 DNA glycosylase activity.
Cockayne Syndrome
Neil2-null Mice Accumulate Oxidized DNA Bases in the Transcriptionally Active Sequences of the Genome and Are Susceptible to Innate Inflammation.
Colonic Neoplasms
DNA polymerase beta expression differences in selected human tumors and cell lines.
Colorectal Neoplasms
Evaluation of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes in familial colorectal cancer predisposition.
Colorectal Neoplasms
Genetic variations in 3'UTRs of SMUG1 and NEIL2 genes modulate breast cancer risk, survival and therapy response.
Colorectal Neoplasms
Sirt3 regulates the level of mitochondrial DNA repair activity through deacetylation of NEIL1, NEIL2, OGG1, MUTYH, APE1 and LIG3 in colorectal cancer.
Cryptorchidism
Effect of busulphan treatment and elevated temperature on the expression of the beta-pol gene in rat testis.
dna 5'-deoxyribose phosphate lyase deficiency
Cells deficient in DNA polymerase beta are hypersensitive to alkylating agent-induced apoptosis and chromosomal breakage.
dna 5'-deoxyribose phosphate lyase deficiency
The deoxyribose phosphate lyase of DNA polymerase ? suppresses a processive DNA synthesis to prevent trinucleotide repeat instability.
Glioma
Elevated expression of DNA polymerase beta gene in glioma cell lines with acquired resistance to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3- nitrosourea.
Hepatitis C
Polymorphisms of base-excision repair genes and the hepatocarcinogenesis.
Herpes Simplex
The replicative DNA polymerase of herpes simplex virus 1 exhibits apurinic/apyrimidinic and 5'-deoxyribose phosphate lyase activities.
Hypersensitivity
Base excision repair intermediates induce p53-independent cytotoxic and genotoxic responses.
Hypersensitivity
Cells deficient in DNA polymerase beta are hypersensitive to alkylating agent-induced apoptosis and chromosomal breakage.
Hypersensitivity
Hypersensitivity of DNA polymerase beta null mouse fibroblasts reflects accumulation of cytotoxic repair intermediates from site-specific alkyl DNA lesions.
Hypersensitivity
Identification of small molecule synthetic inhibitors of DNA polymerase beta by NMR chemical shift mapping.
Hypersensitivity
Mammalian DNA beta-polymerase in base excision repair of alkylation damage.
Hypersensitivity
The lyase activity of the DNA repair protein beta-polymerase protects from DNA-damage-induced cytotoxicity.
Infections
Helicobacter pylori infection downregulates the DNA glycosylase NEIL2, resulting in increased genome damage and inflammation in gastric epithelial cells.
Infections
Roles of conserved residues within the pre-NH2-terminal domain of herpes simplex virus 1 DNA polymerase in replication and latency in mice.
Infections
The DNA Glycosylase NEIL2 Suppresses Fusobacterium-Infection-Induced Inflammation and DNA Damage in Colonic Epithelial Cells.
Infections
The HIV-1 transactivator protein Tat is a potent inducer of the human DNA repair enzyme beta-polymerase.
Lung Neoplasms
Increased risk of lung cancer associated with a functionally impaired polymorphic variant of the human DNA glycosylase NEIL2.
Lung Neoplasms
NEIL2 Protects against Oxidative DNA Damage Induced by Sidestream Smoke in Human Cells.
Lymphoma
The HIV-1 transactivator protein Tat is a potent inducer of the human DNA repair enzyme beta-polymerase.
Lymphoma, AIDS-Related
The HIV-1 transactivator protein Tat is a potent inducer of the human DNA repair enzyme beta-polymerase.
Nasopharyngeal Carcinoma
Salinomycin enhances radiotherapy sensitivity and reduces expressions of BIRC5 and NEIL2 in nasopharyngeal carcinoma.
Neoplasms
Abnormal Expressions of DNA Glycosylase Genes NEIL1, NEIL2, and NEIL3 Are Associated with Somatic Mutation Loads in Human Cancer.
Neoplasms
Alternative splicing of DNA polymerase beta mRNA is not tumor-specific.
Neoplasms
Cervical carcinoma risk associate with genetic polymorphisms of NEIL2 gene in Chinese population and its significance as predictive biomarker.
Neoplasms
DNA polymerase beta expression differences in selected human tumors and cell lines.
Neoplasms
DNA polymerases during tumor growth.
Neoplasms
Elevated expression of DNA polymerase beta gene in glioma cell lines with acquired resistance to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3- nitrosourea.
Neoplasms
Folate deficiency provides protection against colon carcinogenesis in DNA polymerase {beta} haploinsufficient mice.
Neoplasms
Functional variants of the NEIL1 and NEIL2 genes and risk and progression of squamous cell carcinoma of the oral cavity and oropharynx.
Neoplasms
Genetic variations in 3'UTRs of SMUG1 and NEIL2 genes modulate breast cancer risk, survival and therapy response.
Neoplasms
Genomic landscape of DNA repair genes in cancer.
Neoplasms
Haploinsufficiency in DNA polymerase beta increases cancer risk with age and alters mortality rate.
Neoplasms
Identification of novel mRNA isoforms for human DNA polymerase beta.
Neoplasms
PEG-functionalized zinc oxide nanoparticles induce apoptosis in breast cancer cells through reactive oxygen species-dependent impairment of DNA damage repair enzyme NEIL2.
Neoplasms
Regulated over-expression of DNA polymerase beta mediates early onset cataract in mice.
Neoplasms
Sirt3 regulates the level of mitochondrial DNA repair activity through deacetylation of NEIL1, NEIL2, OGG1, MUTYH, APE1 and LIG3 in colorectal cancer.
Neoplasms
Transcriptional upregulation of DNA polymerase beta by TEIF.
Neoplasms
Unique Structural Features of Mammalian NEIL2 DNA Glycosylase Prime Its Activity for Diverse DNA Substrates and Environments.
Neoplasms
Viral integration in BK polyomavirus-associated urothelial carcinoma in renal transplant recipients: multistage carcinogenesis revealed by next-generation virome capture sequencing.
Neuroblastoma
Specific Inhibition of NEIL-initiated repair of oxidized base damage in human genome by copper and iron: potential etiological linkage to neurodegenerative diseases.
Oropharyngeal Neoplasms
Functional variants of the NEIL1 and NEIL2 genes and risk and progression of squamous cell carcinoma of the oral cavity and oropharynx.
Ovarian Neoplasms
DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
Prion Diseases
DNA glycosylase Neil2 contributes to genomic responses in the spleen during clinical prion disease.
Rectal Neoplasms
REG4, NEIL2, and BIRC5 gene expression correlates with gamma-radiation sensitivity in patients with rectal cancer receiving radiotherapy.
Stomach Neoplasms
Genetic Variation of BCL2 (rs2279115), NEIL2 (rs804270), LTA (rs909253), PSCA (rs2294008) and PLCE1 (rs3765524, rs10509670) Genes and Their Correlation to Gastric Cancer Risk Based on Universal Tagged Arrays and Fe3O4 Magnetic Nanoparticles.
Stomach Neoplasms
Polymorphisms in NEIL-2, APE-1, CYP2E1 and MDM2 Genes are Independent Predictors of Gastric Cancer Risk in a Northern Jiangsu Population (China).
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0.00021 - 0.0022
25-mer-deoxyoligonucleotide 3'-labeled uracil-containing DNA duplex
-
0.00045
28-mer deoxyoligonucleotide with a 5' uracil residue
-
pretreated with Eschericia coli uracil N-glycosylase, with concentrations 0.1-2.0 microMol, kcat/Km: 0.24 microMol/min
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0.009 - 0.0097
35-bp-deoxyoligonucleotide duplex containing a uracil residue at position 15
-
0.0005
DNA with a 5'-incised apurinic/apyrimidinic site at position 21
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dRP lyase activity of beta-pol. To quantify the kinetic parameters for the release of deoxyribose phosphate from a preincused apurinic/apyrimidinic site-containing DNA, deoxyribose phosphate is examined as a function of apurinic/apyrimidinic site concentration. The catalytic efficiency results in a kcat/Km: 0.00015 mM/s. The catalytic efficiency of the 8-kDa amino-terminal domain is 7fold lower than that of the intact 39-kDa beta-pol
-
0.0018
mimic of a preincised DNA duplex with a 5'dRP at the site of the nick
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pH 7.5, 37°C
-
0.0006 - 0.007
preincised apurinic/apyrimidinic DNA
-
additional information
intact apurinic/apyrimidinic site
-
0.00021
25-mer-deoxyoligonucleotide 3'-labeled uracil-containing DNA duplex
-
NEIL1
-
0.0022
25-mer-deoxyoligonucleotide 3'-labeled uracil-containing DNA duplex
-
NEIL2
-
0.009
35-bp-deoxyoligonucleotide duplex containing a uracil residue at position 15
-
full-length 290-kDa Pol theta, pH 7.5, 37°C, kcat/Km: 0.047 microM/min
-
0.0097
35-bp-deoxyoligonucleotide duplex containing a uracil residue at position 15
-
98-kDa fragment of Pol theta, pH 7.5, 37°C, kcat/Km: 0.072 microM/min
-
0.0006
preincised apurinic/apyrimidinic DNA
-
pH 7.4, 37°C, in presence of 0.2 mM EDTA
-
0.007
preincised apurinic/apyrimidinic DNA
-
recombinant protein, pH 7.4, 37°C, in presence of 0.2 mM EDTA
-
additional information
intact apurinic/apyrimidinic site
-
similar to that of preincised apurinic/apyrimidinic site
-
additional information
additional information
-
kinetic analysis of dRP lyase activity of the C-terminal domain of Rev1 using a 34-bp duplex DNA substrate. The substrate contained an 18mer DNA strand with 6-FAM at the 3'- end and 5'-RP flap at the margin of a single-nucleotide gap
-
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0.0018
28-mer deoxyoligonucleotide with a 5' uracil residue
-
pretreated with Eschericia coli uracil N-glycosylase, with concentrations 0.1-2.0 microMol, kcat/Km: 0.24 microMol/min
-
0.007 - 0.01167
35-bp-deoxyoligonucleotide duplex containing a uracil residue at position 15
-
0.0075
DNA with a 5'-incised apurinic/apyrimidinic site at position 21
-
dRP lyase activity of beta-pol. To quantify the kinetic parameters for the release of deoxyribose phosphate from a preincused apurinic/apyrimidinic site-containing DNA, deoxyribose phosphate is examined as a function of apurinic/apyrimidinic site concentration. The catalytic efficiency results in a kcat/Km: 0.00015 mM/s. The catalytic efficiency of the 8-kDa amino-terminal domain is 7fold lower than that of the intact 39-kDa beta-pol
-
0.0075
mimic of a preincised DNA duplex with a 5'dRP at the site of the nick
-
pH 7.5, 37°C
-
0.0043 - 4.5
preincised apurinic/apyrimidinic DNA
-
additional information
intact apurinic/apyrimidinic site
-
200fold lower compared to preincised apurinic/apyrimidinic site as substrate
-
0.007
35-bp-deoxyoligonucleotide duplex containing a uracil residue at position 15
-
full-length 290-kDa Pol theta, pH 7.5, 37°C, kcat/Km: 0.047 microM/min
-
0.01167
35-bp-deoxyoligonucleotide duplex containing a uracil residue at position 15
-
98-kDa fragment of Pol theta, pH 7.5, 37°C, kcat/Km: 0.072 microM/min
-
0.0043
preincised apurinic/apyrimidinic DNA
-
pH 7.4, 37°C, in presence of 0.2 mM EDTA
-
4.5
preincised apurinic/apyrimidinic DNA
-
recombinant protein, pH 7.4, 37°C, in presence of 0.2 mM EDTA
-
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metabolism
because DNA polymerase lambda (PolL) belongs to the same family X and has similarities in activity and structure to PolB, PolL may play a backup role in the absence of PolB
evolution
AtPolIs are functionally equipped to play a role in short-patch BER suggesting a major role of AtPolIB in a predicted long-patch BER sub-pathway. The acquisition of insertion 1 in the polymerization domain of AtPolIs is a key component in their evolution as BER associated and replicative DNAPs
evolution
-
enzyme Rev1 is a member of the Y-family of DNA polymerases. Characterization of Rev1 domains in relation to BER activities
malfunction
Detection of stable DNA-protein crosslinks (DPC) between Pol beta and dL in intact cells. Formation of BER-mediated DNA-protein crosslinks, formation of oxidative polbeta-DPC in vivo. Pol beta-DPC are subsequently targeted for ubiquitylation and rapid proteolysis, which is expected to generate 5'-peptidyl-dL-DNA adducts. Inhibition of theproteasome prevents removal of Pol beta-DPC (3B), leading to their toxic accumulation with cell killing and perhaps other consequences. Mitochondrial DNA polymerase gamma (Pol gamma), which harbors a 5'-dRp lyase similar to that of Pol beta, is also trapped by 5'-dL
malfunction
mouse embryonic fibroblasts (MEFs) deficient in enzyme PolB show significantly increased sensitivity to methyl methanesulfonate (MMS). PolB deficiency results in an increased apoptotic cell fraction and chromosomal aberrations after MMS treatment. MMS hypersensitivity can be reversed by the dRP lyase domain of PolB, this hypersensitivity is mainly caused by Sn-BER deficiency. A contribution of PolB-independent repair mechanisms is also likely because of the increased sensitivity of PolB-knockout MEFs at relatively high MMS concentrations
malfunction
three Pol beta enzymes modified at position 72 with aminooxy or hydrazinyl analogues of lysine form transient covalent bonds with the 5'-dRP moiety of the damaged DNA, in the form of an oxime or hydrazone, respectively. Both types of enzyme DNA intermediates are ultimately resolved by the lyase activities of each of the modified enzymes. The formation and resolution of these E-S complexes proceed with diminished kinetics, and with an altered pH profile compared to wild-type. Comparison of base excision repair (BER) reaction with wild-type and modified Pol beta enzymes: while the wild-type enzyme performs BER very efficiently, the BER activity of the three modified enzymes is greatly reduced. The overall BER efficiency of our modified Pol beta enzymes reflects predominantly their ability to remove the 5'-dRP group, the modified proteins demonstrate poor lyase activity
physiological function
-
accurate and efficient repair by nonhomologous end joining NHEJ of double-strand breaks with such damage similarly requires 5'-deoxyribose phosphate/abasic lyase activity provided by Ku70. Ku70 nicks DNA 3' of an abasic site by a mechanism involving a Schiff base covalent intermediate with the abasic site. Ku70 is essential for efficient removal of abasic sites near double strand breaks and, consistent with this result, joining of such breaks is specifically reduced in cells complemented with a lyase-attenuated Ku mutant
physiological function
isoform POLB expression rescues methyl methanesulfonate sensitivity in aprataxin (hnt3)- and FEN1 (rad27)-deficient yeast. Model suggests that aprataxin hydrolyzes the 5'-AMP group and allows for renewed attempts at processing of the repair intermediate, and the 5'-deoxyribose phosphate may be channeled into the normal base excision repair pathway for isoform POLB deoxyribose phsosphate removal and gap filling. In long-path base excision repair, the blocking intermediates can be processed via flap excision by FEN1. In an alternative mechanism, POLB could play a part by direct removal of the entire 5'-AMP-deoxyribose phosphate blocking group via its deoxyribose phosphate lyase activity
physiological function
DNA polymerase beta (Pol beta) is a key enzyme in mammalian base excision repair (BER), contributing stepwise 5'-deoxyribose phosphate (dRP) lyase and gap-filling DNA polymerase activities. The lyase reaction is believed to occur via a beta-elimination reaction following the formation of a Schiff base between the dRP group at the pre-incised apurinic/apyrimidinic site and the epsilon-amino group of Lys72
physiological function
DNA polymerase beta (Pol beta) participates in mammalian base excision repair (BER). The enzyme has a two-domain architecture, reflecting its dual functionality. The polymerase activity, which replaces damaged nucleosides removed during an initial excision process, is within the C-terminal 31 kDa domain, while the N-terminal 8 kDa domain participates in a lyase function, working to remove a 5'-deoxyribose phosphate (5'-dRP) moiety from the damaged DNA substrate
physiological function
DNA polymerase beta (PolB) has both DNA polymerase and dRP lyase activities. Enzyme PolB plays a dominant role in single nucleotide (Sn-) BER by incorporating a nucleotide and removing 5'-dRp. Methyl methanesulfonate (MMS)-induced damage is repaired by Sn-BER
physiological function
DNA polymerase beta (PolB) has both DNA polymerase and dRP lyase activities. Enzyme PolB plays a dominant role in single nucleotide (Sn-) BER by incorporating a nucleotide and removing 5'-dRp. Methyl methanesulfonate (MMS)-induced damage is repaired by Sn-BER. Resistance at low concentrations of MMS is due to an Apex-dependent/PolB-independent repair mechanism
physiological function
oxidized abasic sites are initially incised by Ape1, thus recruiting these lesions into base excision repair (BER) pathways. Lesions such as 2-deoxypentos-4-ulose can be removed by conventional (single-nucleotide) BER, which proceeds through a covalent Schiff base intermediate with DNA polymerase beta (Pol beta) that is resolved by hydrolysis. In contrast, the lesion 2-deoxyribonolactone (dL) must be processed by multinucleotide (long-patch) BER: attempted repair via the single-nucleotide pathway leads to a dead-end, covalent complex with Pol beta cross-linked to the DNA by an amide bond. In classical base excision repair (BER), only the missing nucleotide is replaced by DNA polymerase beta (Pol beta), and the deoxyribose-5'-phosphate (5'-dRp) residue is excised by a 5'-dRp lyase activity in a discrete domain of Pol beta. The result is a nicked DNA that is competent for ligation, usually by DNA ligase III alpha. Another subpathway called long-patch BER (LP-BER) also exists, in which DNA repair synthesis replaces 2-10 nucleotides, Fen1 (flap) endonuclease excises the displaced strand, and DNA ligase I seals the nick. LP-BER repair synthesis can be initiated by Pol beta, which may (inefficiently) insert a second nucleotide. When the 5'-dRp strand is displaced by two or more nucleotides, the 5'-dRp lyase of Pol beta no longer functions, requiring Fen1 to remove the single-stranded flap. BER processing of oxidative DNA damage and the formation of DNA-protein crosslinks (DPC), overview
physiological function
plant organelles repair damaged DNA using the multi-enzyme base excision repair (BER) pathway. The initial enzymatic steps in BER produce a 5'-deoxyribose phosphate (5'-dRP) moiety that must be removed to allow DNA ligation. DNA polymerases (DNAPs) remove the 5'-dRP moiety using their intrinsic lyase and/or strand-displacement activities during short or long-patch BER sub-pathways, respectively. Arabidopsis thaliana encodes two family-A DNAPs paralogues, AtPolIA and AtPolIB, which are the sole DNAPs in plant organelles identified to date. Both AtPolIs present 5'-dRP lyase activities. AtPolIB performs efficient strand-displacement on a BER-associated 1-nt gap DNA substrate, whereas AtPolIA exhibits only moderate strand-displacement activity. Both lyase and strand-displacement activities are dependent on an amino acid insertion that is exclusively present in plant organellar DNAPs. AtPolIs contribute to long-patch BER by strand-displacement synthesis, but AtPolIs catalyze long and short-patch BER
physiological function
-
Rev1 is a base excision repair enzyme with 5'-deoxyribose phosphate lyase activity, dRP lyase activity of the C-terminal domain of Rev1. Rev1 also has deoxycytidyl transferase activity (EC 2.7.7.-) that incorporates dCMP into DNA and its ability to function as a scaffold factor for other Y-family polymerases in translesion bypass events. Rev1 also is involved in mutagenic processes during somatic hypermutation of immunoglobulin genes. Mouse fibroblast cells lacking pol beta have a DNA repair deficiency and a phenotype of elevated methyl methanesulfonate (MMS)-induced mutations. Enzyme Rev1 is strictly required for the elevated MMS-induced mutagenesis phenotype as observed in the pol beta null background, mechanisms of the Rev1-mediated MMS-induced mutagenesis, overview
additional information
residue AtPollB-Lys593 acts as nucleophile for lyase activity and is responsible for 5'-RP lyase activity in AtPolIB. 5'-RP lyase activity is mapped to a single amino acid in insertion 1
additional information
residue AtPollB-Lys593 acts as nucleophile for lyase activity and is responsible for 5'-RP lyase activity in AtPolIB. 5'-RP lyase activity is mapped to a single amino acid in insertion 1
additional information
-
residue AtPollB-Lys593 acts as nucleophile for lyase activity and is responsible for 5'-RP lyase activity in AtPolIB. 5'-RP lyase activity is mapped to a single amino acid in insertion 1
additional information
study of the lyase activity of human DNA polymerase beta using analogues of the intermediate Schiff base complex
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monomer
-
1 * 45000, SDS-PAGE, wild-type mitochondrial pol beta and K72A mutant
monomer
-
1 * 39000, consists of a 31 kDa C-terminal and a 8 kDa amino-terminal domain
additional information
-
alignment with the rat nuclear enzyme shows that the mitochondrial pol beta contains the essential conserved amino acids Lys35, Lys60, Lys68, and Lys72
additional information
-
dRP lyase activity is intrinsic to the catalytic subunit of human pol gamma
additional information
-
polymerase theta is a ca. 300 kDa polypetide. The 98-kDa C-terminal region possesses both the DNA polymerase and the dRP lyase activity. The 5'-dRP lyase activity is independent of the polymerase activity. The polymerase inactive mutant D829N/E830Q retains full 5'-dRP lyase activity. Domain mapping of the 98-kDa enzyme reveals that the 5'-dRP lyase active site resides in a 24-kDa-domain
additional information
-
the catalytic subunit of the HSV-1 DNA polymerase exhibits apurinic/apyrimidinic and 5'-deoxyribose phosphate lyase activities
additional information
the 8-kDa domain of polymerase beta is responsible for single-stranded DNA binding, 5'-phosphate recognition, and dRP lyase activity, formed by the amino acid residues 1-91 of Li Polbeta. The residues Tyr39, Lys60, Lys68, Lys72, Glu75, and Glu84 play a role in the catalysis. Lys72, identified as the nucleophile in Polbeta is responsible for Schiff base forming during beta-elimination of the dRP moiety
additional information
-
the 8-kDa domain of polymerase beta is responsible for single-stranded DNA binding, 5'-phosphate recognition, and dRP lyase activity, formed by the amino acid residues 1-91 of Li Polbeta. The residues Tyr39, Lys60, Lys68, Lys72, Glu75, and Glu84 play a role in the catalysis. Lys72, identified as the nucleophile in Polbeta is responsible for Schiff base forming during beta-elimination of the dRP moiety
additional information
-
Rev1 domain mapping of the C-terminal domain by limited proteolysis
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K72A
-
PCR-based site-directed mutagenesis, deficient in forming a Schiff base intermediate and accumulating an enzyme dRP intermediate without releasing free dRP
D829N/E830Q
-
the polymerase inactive mutant D829N/E830Q retains full 5'-dRP lyase activity. Domain mapping of the 98-kDa enzyme reveals that the 5'-dRP lyase active site resides in a 24-kDa-domain
E71Q
retains wild-type enzyme activity
E75A
about 75% of wild-type enzyme activity
F25W
about 85% of wild-type enzyme activity
H34G
about 45% of wild-type enzyme activity
K310A
eliminates more than 90% of the wild-type dRP lyase activity, indicating that Lys 310 is the main nucleophile involved in the reaction, forming the Schiff base internediate during beta-elimination
K35A/K68A
part of the active site, similar to wild-type enzyme activity
K35A/K72A
part of the active site, above 95% loss of enzyme activity
K35R
part of the active site, no effect on enzyme activity
K35R/K68R/K72R
part of the active site, above 95% loss of enzyme activity
K60A
about 40% of wild-type enzyme activity
K68A/E71Q
retains wild-type enzyme activity
K68A/K72A
about 10% of wild-type enzyme activity
K68R
part of the active site, significant reduction of enzyme activity
K72R
part of the active site, above 95% loss of enzyme activity
K84A
retains wild-type enzyme activity
Y39F
part of the active site, similar to wild-type enzyme activity
D256A
-
site-directed mutagenesis, C-terminal polymerase domain, completely eliminates dRP lyase activity, proficient in DNA synthesis by the polymerase reaction
K35A/K68A/K72A
-
site-directed mutagenesis, amino-terminal dRP lyase domain, completely eliminates dRP lyase activity, proficient in DNA synthesis by the polymerase reaction
K35A/K68A/K72A/D256A
-
site-directed mutagenesis, amino-terminal dRP lyase domain, deficient in dRP lyase and polymerase activity
R283A
-
site-directed mutagenesis, C-terminal polymerase domain, deficient in base excision repair DNA synthesis activity of the polymerase, but has full dRP lyase activity
K552A
site-directed mutagenesis matching the active site of polbeta. The mutant Trf4K552A is overexpressed in a trf4DELTA mutant. The overproduction of Trf4 wild-type increases methylmethane sulfonate resistance similar to that of of the wild-type. The Trf4K552A mutant exhibits hypersensitivity to methylmethane sulfonate, causing double-stranded DNA breaks
K35A
about 50% of wild-type enzyme activity, Lys72 and Lys35 are involved in the dRP lyase reaction catalyzed by the 8-kDa domain and Lys35 is involved in 5'-phosphate recognition. Lys35 may stabilize the leaving group in the dRP lyase reaction through its interaction with the 5'-phosphate of the DNA-terminus
K35A
part of the active site, 50% loss of enzyme activity
K35A/K68A/K72A
devoid of dRP lyase, Lys72 and Lys35 are involved in the dRP lyase reaction catalyzed by the 8-kDa domain and Lys35 is involved in 5'-phosphate recognition. Lys35 may stabilize the leaving group in the dRP lyase reaction through its interaction with the 5'-phosphate of the DNA-terminus
K35A/K68A/K72A
part of the active site, above 95% loss of enzyme activity
K68A
part of the active site, stimulation of enzyme activity
K68A
retains wild-type enzyme activity
K68A
mutation has no significant effect on the removal of 5'-AMP-deoxyribose phosphate
K72A
-
2 mM pyridoxal 5'-phosphate, the mutant K72A of the 8-kDa domain and the full-lenghth protein beta-pol exhibit 90 and 80% loss of activity, respectively
K72A
less than 10% of wild-type enzyme activity, Lys72 and Lys35 are involved in the dRP lyase reaction catalyzed by the 8-kDa domain and Lys35 is involved in 5'-phosphate recognition. Lys35 may stabilize the leaving group in the dRP lyase reaction through its interaction with the 5'-phosphate of the DNA-terminus
K72A
-
mutant is not able to exhibit short-patch repair mechanism
K72A
part of the active site, above 95% loss of enzyme activity
additional information
construction of several AtPolIB and deletion mutants, AtPolIB exo-DELTAins1, AtPolIB exo-DELTAins2, and AtPolIB exo-DELTAins3, AtPolIB exo- and polymerase mutants harboring deletions in insertion 1, 2 or 3, the mutants, especially AtPolIB exo-DELTAins1 and 3 insertion mutants, shows reduced activity compared to wild-type. Deletions in AtPolIB decrease strand-displacement activities
additional information
construction of several AtPolIB and deletion mutants, AtPolIB exo-DELTAins1, AtPolIB exo-DELTAins2, and AtPolIB exo-DELTAins3, AtPolIB exo- and polymerase mutants harboring deletions in insertion 1, 2 or 3, the mutants, especially AtPolIB exo-DELTAins1 and 3 insertion mutants, shows reduced activity compared to wild-type. Deletions in AtPolIB decrease strand-displacement activities
additional information
-
construction of several AtPolIB and deletion mutants, AtPolIB exo-DELTAins1, AtPolIB exo-DELTAins2, and AtPolIB exo-DELTAins3, AtPolIB exo- and polymerase mutants harboring deletions in insertion 1, 2 or 3, the mutants, especially AtPolIB exo-DELTAins1 and 3 insertion mutants, shows reduced activity compared to wild-type. Deletions in AtPolIB decrease strand-displacement activities
additional information
the lyase catalytic pocket, Lys72, is replaced with each of several nonproteinogenic lysine analogues. The modified Pol beta enzymes are produced by coupled in vitro transcription and translation from a modified DNA template containing a TAG codon at the position corresponding to Lys72. In the presence of a misacylated tRNACUA transcript, suppression of the UAG codon in the transcribed mRNA leads to elaboration of full-length Pol beta having a lysine analogue at position 72. Replacement of the primary nucleophilic amine with a secondary amine in the form of N-methyllysine affects mainly the stability of the Schiff base intermediate and results in relatively moderate inhibition of lyase activity and BER. Elongation of the side chain of the catalytic residue by one methylene group, achieved by introduction of homolysine at position 72, apparently shifts the amino group to a position less favorable for Schiff base formation. This effect is attenuated when the side chain is elongated by replacing one side-chain methylene group with a bridging S atom (thialysine). In comparison, replacement of lysine 72 with an analogue having a guanidine moiety in lieu of an epsilon-amino group (homoarginine) or a sterically constrained secondary amine (piperidinylalanine) leads to almost complete suppression of dRP excision activity and the ability of Pol beta to support BER
additional information
-
an active-site deletion mutant of beta-pol, in which residues within the C-terminal portion, residues 263-335 that are required for DNA synthesis are deleted, completely deficient in single-nucleotide base excision repair DNA synthesis, but active in 5'-deoxyribose phosphate removal
additional information
construction of PolB-knockout mouse embryonic fibroblasts (MEFs)Mbeta19tsA, phenotype. Mouse embryonic fibroblasts (MEFs) deficient in enzyme PolB show significantly increased sensitivity to methyl methanesulfonate (MMS). Wild-type MEFs and PolB-knockout MEFs are transfected with shRNA-expression vectors for Apex knockdown. Apex knockdown has essentially no effect on cell viability in the presence or absence of PolB. Thus, Apex knockdown does not affect the number of viable cells immediately after MMS treatment. The MMS sensitivity depends on Apex protein levels and suggest that resistance at low concentrations of MMS is due to an Apex-dependent/PolB-independent repair mechanism
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codon-optimized gene POLB, recombinant expression of C-terminally His6-tagged wild-type and mutant enzymes in Escherichia coli
expressed in Escherichia coli and purified
-
expressed in Escherichia coli BL21(DE3) via electroporation, lacking the 9-amino acid mitochondrial targeting signal sequence
-
expressed in Escherichia coli strain BL21 (DE3) competent cells
-
expressed in MB36.3 cell, wild-type, SV40 T-Ag transformed cell line haboring the lambda phage transgene lambdaLIZ
-
expressed in Spodoptera friguperda
-
expresses in Escherichia coli M15 (pREP4). The protein aggregates as inclusion bodies, solubilized in 5 M guanidinium hydrochloride and 20 mM inidazole-HCl, pH 8.0 and purified
expression of mutant enzymes by coupled in vitro transcription and translation from a modified DNA template containing a TAG codon at the position corresponding to Lys72
gene Rev1, recombinant expression of His-tagged full-length enzyme in in Escherichia coli
-
MB38DELTA4, beta-pol null, sensitive to the methylating agent methylmethanesulfonate, SV40 T-Ag transformed cell line haboring the lambda phage transgene lambdaLIZ
-
recombinant pol lambda and the K310A mutant are overexpressed in Eschercihia coli and purified to near homogeneity
recombinant wild-type and mutant proteins H34G, K35A, K35R, Y39F, K68A, K68R, K72A, K72R, K35A/K68A, K35A/K72A, K35A/K68A/K72A, K35R/K68R/K72R are expressed in Escherichia coli and purified
the 98-kDa-fragment and the mutant D829N/E830Q enzyme are overexpressed in Escherichia coli BL21-CodonPlus-RP-cells
-
the mutants K72A, K68A/K72A, K35A, K60A, H34G, E75A, F25W, K68A, K84A, E71Q, and K68A/E71Q are expressed in Escherichia coli, and the recombinant proteins are purified to near homogeneity, to 95%. Mutant proteins show similar behaviour to wild-type protein, indicating less changes in structural properties
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Prasad, R.; Batra, V.K.; Yang, X.P.; Krahn, J.M.; Pedersen, L.C.; Beard, W.A.; Wilson, S.H.
Structural insight into the DNA polymerase beta deoxyribose phosphate lyase mechanism
DNA Repair
4
1347-1357
2005
Homo sapiens (P06746)
brenda
Alonso, A.; Terrados, G.; Picher, A.J.; Giraldo, R.; Blanco, L.; Larraga, V.
An intrinsic 5'-deoxyribose-5-phosphate lyase activity in DNA polymerase beta from Leishmania infantum supports a role in DNA repair
DNA repair
5
89-101
2006
Leishmania infantum (Q9U6N3), Leishmania infantum
brenda
Gellon, L.; Carson, D.R.; Carson, J.P.; Demple, B.
Intrinsic 5'-deoxyribose-5-phosphate lyase activity in Saccharomyces cerevisiae Trf4 protein with a possible role in base excision DNA repair
DNA Repair
7
187-198
2008
Saccharomyces cerevisiae (P53632), Saccharomyces cerevisiae
brenda
Lopes, D.d.O.; Schamber-Reis, B.L.F.; Regis-da-Silva, C.G.; Rajao, M.A.; DaRocha, W.D.; Macedo, A.M.; Franco, G.R.; Nardelli, S.C.; Schenkman, S.; Hoffmann, J.-S.; Cazaux, C.; Pena, S.D.J.; Teixeira, S.M.R.; Machado, C.R.
Biochemical studies with DNA polymerase beta and DNA polymerase beta -PAK of Trypanosoma cruzi suggest the involvement of these proteins in mitochondrial DNA maintenance
DNA Repair
7
1882-1892
2008
Trypanosoma cruzi
brenda
Allinson, S.L.; Dianova, II; Dianov, G.L.
DNA polymerase beta is the major dRP lyase involved in repair of oxidative base lesions in DNA by mammalian cell extracts
EMBO J.
20
6919-6926
2001
Homo sapiens
brenda
Grin, I.R.; Khodyreva, S.N.; Nevinsky, G.A.; Zharkov, D.O.
Deoxyribophosphate lyase activity of mammalian endonuclease VIII-like proteins
FEBS Lett.
580
4916-4922
2006
Mus musculus
brenda
Prasad, R.; Beard, W.A.; Chyan, J.Y.; Maciejewski, M.W.; Mullen, G.P.; Wilson, S.H.
Functional analysis of the amino-terminal 8-kDa domain of DNA polymerase beta as revealed by site-directed mutagenesis. DNA binding and 5'-deoxyribose phosphate lyase activities
J. Biol. Chem.
273
11121-11126
1998
Homo sapiens (P06746)
brenda
Prasad, R.; Beard, W.A.; Strauss, P.R.; Wilson, S.H.
Human DNA polymerase beta deoxyribose phosphate lyase. Substrate specificity and catalytic mechanism
J. Biol. Chem.
273
15263-15270
1998
Homo sapiens
brenda
Garcia-Diaz, M.; Bebenek, K.; Kunkel, T.A.; Blanco, L.
Identification of an intrinsic 5'-deoxyribose-5-phosphate lyase activity in human DNA polynmerase lambda. A possible role in base excision repair
J. Biol. Chem.
276
34659-34663
2001
Homo sapiens (Q9UGP5), Homo sapiens
brenda
Saxowsky, T.T.; Matsumoto, Y.; Englund, P.T.
The mitochondrial DNA polymerase beta from Crithdia fasciculata has a 5'-deoxyribose phosphate (dRP) lyase activity but is deficient in the release of dRP
J. Biol. Chem.
277
37201-37206
2002
Crithidia fasciculata
brenda
Wong, D.; Demple, B.
Modulation of the 5'-deoxyribose-5-phosphate lyase and DNA synthesis activities of mammalian DNA polymerase beta by apurinic/apyrimidinic endonuclease 1
J. Biol. Chem.
279
25268-25275
2004
Homo sapiens
brenda
Maciejewski, M.W.; Liu, D.; Prasad, R.; Wilson, S.H.; Mullen, G.P.
Backbone dynamics and refined solution structure of the N-terminal domain of DNA polymerase beta. Correlation with DNA binding and dRP lyase activity
J. Mol. Biol.
296
229-253
2000
Rattus norvegicus
brenda
Sobol, R.W.; Prasad, R.; Evenski, A.; Baker, A.; Yang, X.P.; Horton, J.K.; Wilson, S.H.
The lyase activity of the DNA repair protein beta-polymerase protects from DNA-damage-induced cytotoxicity
Nature
405
807-810
2000
Mus musculus
brenda
Prasad, R.; Longley, M.J.; Sharief, F.S.; Hou, E.W.; Copeland, W.C.; Wilson, S.H.
Human DNA polymerase theta possesses 5'-dRP lyase activity and functions in single-nucleotide base excision repair in vitro
Nucleic Acids Res.
37
1868-1877
2009
Homo sapiens
brenda
Bogani, F.; Boehmer, P.E.
The replicative DNA polymerase of herpes simplex virus 1 exhibits apurinic/apyrimidinic and 5-deoxyribose phosphate lyase activities
Proc. Natl. Acad. Sci. USA
105
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