2.3.1.48: histone acetyltransferase
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For detailed information about histone acetyltransferase, go to the full flat file.
Word Map on EC 2.3.1.48
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2.3.1.48
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rhythm
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oscillation
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suprachiasmatic
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chromatin
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entrain
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night
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scn
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sleep
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melatonin
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drosophila
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diurnal
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pacemaker
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locomotor
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light-dark
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nuclei
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deacetylases
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pineal
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morning
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photoperiodic
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retinal
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draw
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hypothalamus
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hdacs
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light-induced
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melanogaster
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photoreceptors
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noise
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bayesian
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nocturnal
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evening
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daytime
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deacetylation
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coherent
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co-activator
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oscillatory
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dementia
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transactivation
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flies
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neuropeptide
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wake
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schedule
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24-hour
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pulses
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circuit
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medicine
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molecular biology
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mood
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verbal
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neuropsychological
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drug development
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tick
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analysis
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pharmacology
- 2.3.1.48
- rhythm
-
oscillation
-
suprachiasmatic
- chromatin
-
entrain
-
night
- scn
- sleep
- melatonin
- drosophila
-
diurnal
-
pacemaker
-
locomotor
-
light-dark
- nuclei
- deacetylases
-
pineal
-
morning
-
photoperiodic
- retinal
-
draw
- hypothalamus
- hdacs
-
light-induced
- melanogaster
- photoreceptors
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noise
-
bayesian
-
nocturnal
-
evening
-
daytime
-
deacetylation
-
coherent
-
co-activator
-
oscillatory
- dementia
-
transactivation
- flies
-
neuropeptide
-
wake
-
schedule
-
24-hour
-
pulses
-
circuit
- medicine
-
lengthen
- molecular biology
-
trichostatin
-
mood
-
verbal
-
neuropsychological
- drug development
- tick
- analysis
- pharmacology
Reaction
Synonyms
AAPatA, acetyltransferase, histone, Ada2/Ada3/Gcn5 complex, AIB1, amino acid sensing acetyltransferase, AmiPatA, Amir 5672, ARD1, ARD1 acetyltransferase, arginine methyltransferase A, arginine methyltransferase B, arrest defective 1, arrest defective protein 1 acetyltransferase, At3g14980, ATAC2, ATase1, ATase2, cAMP-regulated protein lysine acetyltransferase, Cbp, CBP histone acetyltransferase, CBP/p300, chameau, circadian locomoter output cycles protein kaput, CLOCK, CREB binding protein, CREB-binding protein, CREBBP, east1, ELO3, ELONGATA3, elongator protein 3, ELP3, enhancer-of-asymmetric leaves-two1, Enok, EP300, Esa1, factor acetyltransferase, FAT, Gcn5, GCN5 family KAT, Gcn5 HAT, GCN5 lysine acetyltransferase, GCN5 N acetyltransferase 5, Gcn5 related N-acetyltransferase, GCN5-like acetyltransferase, GCN5-like enzyme, GCN5-related N-acetyltransferase, Gcn5/PCAF histone acetyltransferase, GCN5b, GCN5L2, general control non-derepressible 5, general control non-repressed protein5, general control nonderepressible 5, general control nonrepressed-protein 5, general control of amino acid synthesis 5, GNAT, GNAT-related histone acetyltransferase complex, GTF3C4, H4 lysine acetyltransferase, HAC1, HAG1, HAG3, HAG4, HAG5, HAM1, HAM2, hARD1, HAT, HAT-B, HAT-B complex, Hat1, Hat1p, Hat2, HatB3.I, HBO1, histone (H4 K16) acetyltransferase, histone acetokinase, histone acetyl transferase, histone acetylase, histone acetyltransferase, histone acetyltransferase 1, histone acetyltransferase AtGCN5, histone acetyltransferase B, histone acetyltransferase Tip60, histone acetyltransferase-1, histone acetyltransferases, histone H3 acetyltransferase, histone H4 acetyltransferase, histone H4 lysine 16 acetyltransferase, histone transacetylase, histone/protein lysine acetyltransferase, HIV-1 Tat-interactive protein, hMOF, Hpa2, Hpa3, human acetylase binding to ORC1, Idm1, K (lysine) acetyltransferase 8, K(lysine) acetyltransferase 8, KAT, KAT10, KAT11, KAT12, KAT13A, KAT13B, KAT13C, KAT13D, KAT2, Kat2A, KAT2A/GCN5, Kat2b, KAT3A, KAT3B, KAT4, KAT5, KAT6, KAT6A, KAT6B, KAT7, KAT8, KAT9, Lsy-12, lysine acetyltransferase, lysine acetyltransferase 2, lysine acetyltransferase 2A, lysine acetyltransferase 2B, lysine acetyltransferase 5, lysine acetyltransferase 8, lysine acetyltransferase complex, lysine acetyltransferase p300, lysine acetyltransferases, lysine-acetyltransferase, Mof, monocytic leukemia zinc finger, monocytic leukemia zinc finger protein, More, Morf, MORF histone acetyltransferase, MOZ, MOZ histone acetyltransferase, Moz related factor, Mst1, MtPat, Myb-binding protein 1A, MYBBP1A, MYST, MYST protein lysine acetyltransferase, MYST-related histone acetyltransferase complex, MYST1, MYST2, MYST3, MYST4, N(alpha)-acetyltransferase 10, N-acetyltransferase, N-terminal acetyltransferase, NAA10, NAT, NAT4, NCoA-1, NCoA-3, NCOAT, Nepsilon-lysine acetyltransferase, NuA4, NuA4 histone acetyltransferase, nuclear cytoplasmicO-GlcNAcase and acetyltransferase, nuclear receptor coactivator 1, nuclear receptor coactivator 3, nucleosome-histone acetyltransferase, Nut1, p/CAF, P/CAF histone acetyltransferase, p160, p300, p300 HAT, p300 histone acetyltransferase, p300/CBP, p300/CBP associated factor, p300/CBP histone acetyltransferase, P300/CBP-associated factor, p300/CBP-associated factor (pCAF), p300HAT, PA4534, Pat, PCAF, PCAF histone acetyltransferase, PF11_0192, PfGCN5, PfGCN5 HAT, Piccolo NuA4 complex, protein acetyl-transferase, protein acetyltransferase, Qkf, regulator of Ty1 transposition protein 109, RmtA, RmtB, RPD3, Rtt109, Rv0998, SAS complex, Sas2, Sas3, SRC1, SRC3, Sven 0867, SvePatA, TAF, TAF1, Tat interacting protein of 60 kDa, Tat-interactive protein, 60 kDa, TBP1, TFIIIC90, tGCN5, TgGCN5b, TgMYST-B, Tip60, tumor suppressor histone H3 lysine 23 acetyltransferase, type B histone acetyltransferase, YfmK, zMoz
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2.3.1.48 histone acetyltransferaseAdvanced search results
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results (Engineering
Engineering on EC 2.3.1.48 - histone acetyltransferase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
D924A
mutation in conserved residues in the histone acetyltransferase domain, abolishes the in vitro acetyltransferase activity
E451Stop
mutation results in the silencing of 35S-NPTII but not the RD29A-LUC transgene
E941Q
mutation in conserved residues in the histone acetyltransferase domain, abolishes the in vitro acetyltransferase activity
M942A
mutation in conserved residues in the histone acetyltransferase domain, diminishes the in vitro acetyltransferase activity
G88A
site-directed mutagenesis, yfmKG88A is found to phenocopy the yfmK mutant most closely in vivo. HbsK41Q is able to bypass the yfmKG88A phenotype, suggesting that the cognate protein is catalytically inactive
G88A
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site-directed mutagenesis, yfmKG88A is found to phenocopy the yfmK mutant most closely in vivo. HbsK41Q is able to bypass the yfmKG88A phenotype, suggesting that the cognate protein is catalytically inactive
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E355stop
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site-directed mutagenesis of the Gn5 gene, inactive mutant, the loss of either dGcn5 or dAda2a function results in similar chromosome structural and developmental defects, in dAda2a mutants, the nucleosomal H4 acetylation at lysines 12 and 5 is significantly reduced, while the acetylation established by dAda2b-containing Gcn5 complexes at H3 lysines 9 and 14 is unaffected, overview
C746A
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site-directed mutagenesis, mutation in the HAT domain, leads to only slightly reduced catalytic activity, but highly reduced cyclin D1 transcription in the cells
E742Q
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site-directed mutagenesis, mutation in the HAT domain, leads to only slightly reduced catalytic activity, but highly reduced cyclin D1 transcription in the cells
G485
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a HBO1 mutant, which contains a mutation of an invariant glycine in the histone acetyltransferase domain that abolishes enzymatic activity
G923/925D
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site-directed mutagenesis, mutation in the HAT domain, leads to only slightly reduced catalytic activity, but highly reduced cyclin D1 transcription in the cells
K1358A
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site directed mutagenesis of lysine 1358 of the p300 acetyltransferase domain reveals that inhibitor binds via a hydrogen bond to this lysine residue in the wild-type, in the mutant no binding leads to total loss of acetyltransferase activity
K136R
R82A/Y122F
S1834A
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site-directed mutagenesis, the mutant shows no histone acetylation and ICAM-1 gene expression, overview
S1834E
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site-directed mutagenesis, the mutant shows no histone acetylation and ICAM-1 gene expression, overview
T612G
site-directed mutagenesis, the mutant is able to activate a series of alkynyl and azido acyl-CoA for histone acylation. Residue Thr612 is conserved in the PCAF/GCN5 family
Y1467F
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the mutant shows a 150fold reduction in catalytic activity relative to wild-type enzyme
Y638A
G657E
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site-directed mutagenesis, loss-of-function mutation in the HAT catalytic domain of MOZ, mutation of the HAT catalytic domain affects B-lineage differentiation and hematopoietic stem/progenitor cell frequencies, analysis of hematopoietic cell populations in HAT-/-, HAT-/+, and HAT+/+ mice, overview. The HAT activity of MOZ is essential for maintaining the functionality of hematopoietic stem cells
Y891F
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site-directed mutagenesis, catalytically inactive mutant, stable binding of unacetylated histone H4, useful for purification of the histone protein
G657E
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site-directed mutagenesis, loss-of-function mutation in the HAT catalytic domain of MOZ, mutation of the HAT catalytic domain affects B-lineage differentiation and hematopoietic stem/progenitor cell frequencies, analysis of hematopoietic cell populations in HAT-/-, HAT-/+, and HAT+/+ mice, overview. The HAT activity of MOZ is essential for maintaining the functionality of hematopoietic stem cells
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A190S
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site-directed mutagenesis, mutant of Gcn5, similar kinetics to wild-type
A190T
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site-directed mutagenesis, mutant of Gcn5, decreased Km for acetyl-CoA
C303A
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site-directed mutagenesis of Sas3, exchange in zinc finger motif, remaining activity: 4.5% of wild-type activity
C304A
site-directed mutagenesis, the mutant shows activity and pH-dependence similar to the wild-type enzyme
C304S
C304S/E338Q
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site-directed mutagenesis, the mutant protein is intrinsically unstable and catalytically inactive, the mutant cell is lethal
C306A
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site-directed mutagenesis of Sas3, exchange in zinc finger motif, remaining activity: 11.1% of wild-type activity
C323A
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site-directed mutagenesis of Sas3, exchange in zinc finger motif, no remaining activity
D287A/D288A
mutation does not substantially change the shape of the kcat-pH profile, suggesting these conserved residues do not function as base catalysts for histone acetylation
D287N
mutation does not substantially change the shape of the kcat-pH profile, suggesting these conserved residues do not function as base catalysts for histone acetylation
D288N
mutation does not substantially change the shape of the kcat-pH profile, suggesting these conserved residues do not function as base catalysts for histone acetylation. Mutant reveals a dramatic 1000fold decrease in kcat/Km for acetyl-CoA
D343V
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site-directed mutagenesis, the mutant shows reduced histone H4 acetylation compared to the wild-type Esa1
E173Q
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site-directed mutagenesis, 500-600 decrease in turnover, no effect on substrate binding, Glu173 is the general base catalyst
E299K/E300K/D301K
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similar activity toward H3 in comparison to wild-type enzyme, more than 10fold reduction in activation by chaperone Vps75
E338Q
E374A/E378A
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similar activity toward H3 in comparison to wild-type enzyme
E374K/E378K
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similar activity toward H3 in comparison to wild-type enzyme, more than 10fold reduction in activation by chaperone Vps75
G429E
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site-directed mutagenesis of Sas3, exchange in acetyl-CoA binding motif, no remaining activity
G431A
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site-directed mutagenesis of Sas3, exchange in acetyl-CoA binding motif, nearly no remaining activity: 0.8% of wild-type activity
H319A
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site-directed mutagenesis of Sas3, exchange in zinc finger motif, nearly no remaining activity: 1.2% of wild-type activity
K262R
mutant does not support growth of yeast cells, mutant is catalytically inactive
K428A
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site-directed mutagenesis of Sas3, exchange in acetyl-CoA binding motif, remaining activity: 55.9% of wild-type activity
K56Q
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mutation of the acetylation site of histone H3, the mutant shows CAG repeat contractions similar to the wild-type enzyme
K56R
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mutation of the acetylation site of histone H3, regulation of H3K56 acetylation plays a role in preventing CAG repeat contractions, but may not account for the full effect of deleting the RTT109 gene
L254P
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esa1 mutant (reduced histone H4 acetylation) at 36°C (restrictive temperature) is sensitive to 6-azauracil (inhibitor impeding elongation by lowering nucleotide pools) but shows little effect at 30°C (permissive temperature), gene length dependent defects in transcription
L357H
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site-directed mutagenesis, the mutant shows 41% reduced histone H4 acetylation compared to the wild-type Esa1
Q426A
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site-directed mutagenesis of Sas3, exchange in acetyl-CoA binding motif, remaining activity: 38.6% of wild-type activity
W66R
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site-directed mutagenesis, the mutant shows reduced histone H4 acetylation compared to the wild-type Esa1
Y430A
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site-directed mutagenesis of Sas3, exchange in acetyl-CoA binding motif, remaining activity: 16.7% of wild-type activity
Y430L
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site-directed mutagenesis of Sas3, exchange in acetyl-CoA binding motif, remaining activity: 87.0% of wild-type activity
K56Q
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mutation of the acetylation site of histone H3, the mutant shows CAG repeat contractions similar to the wild-type enzyme
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K56R
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mutation of the acetylation site of histone H3, regulation of H3K56 acetylation plays a role in preventing CAG repeat contractions, but may not account for the full effect of deleting the RTT109 gene
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E703G
the point mutation ablates enzymatic activity, dominant-negative form of GCN5b. Replication arrest observed in ddHAGCN5b(E703G) parasites is due to a reduction in histone acetylation, which in turn leads to dysregulation of the transcriptome
additional information
K136R
site-directed mutagenesis, that lacks autoacetylation, the mutant shows wild-type NAT activity
R82A/Y122F
site-directed mutagenesis, the dominant-negative (DN) mutant lacks acetyltransferase activity. The DN mutant includes two mutations R82A and Y122F, which inhibit the binding of acetyl-CoA to hARD1/NAA10 and consequently suppresses its acetyltransferase activity. The DN mutant fails to acetylate itself
R82A/Y122F
site-directed mutagenesis, the enzyme mutant shows highly reduced lysine acetyltransferase activity with aurora kinase A as substrate
R82A/Y122F
site-directed mutagenesis, the mutant shows highly reduced NAT activity compared to wild-type
Y638A
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mutant of PCAF catalytic domain, increased Km and decreased kcat compared to wild-type
Y638A
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mutant of PCAF catalytic domain, increased Km and decreased kcat compared to wild-type
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C304S
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
C304S
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site-directed mutagenesis, the mutant shows 97.4% reduced histone H4 acetylation at pH 8.0 compared to the wild-type Esa1
E338Q
site-directed mutagenesis, the mutant shows 200fold reduced kcat at pH 7.5 compared to the wild-type enzyme
E338Q
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site-directed mutagenesis, the mutant shows 99.5% reduced histone H4 acetylation at pH 8.0 compared to the wild-type Esa1, recombinant Esa1-E338Q displays detectable HATactivity at elevated pH of 9.2
additional information
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construction of hac1 mutants by T-DNA insertion, lesions in AtHAC1 cause pleiotropic developmental defects, including delayed flowering, a shortened primary root, and partially reduced fertility, phenotypes, overview, mechanism, histone modifications of FLC chromatin are not affected by mutations in HAC1, HAC1 affects flowering time by epigenetic modification of factors upstream of the flowering locus C, overview
additional information
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analysis of T-DNA insertion mutant shows that gcn5 mutation seriously reduces acetylation of histone H3K14 and H3K27
additional information
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using the yeast two-hybrid system it is shown that GCN5 interacts specifically with a phosphatase 2C protein (AtPP2C-6-6). AtPP2C-6-6 may function as a negative regulator of GCN5 activity in Arabidopsis thaliana
additional information
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both male and female Ham1:Ham2 double-mutant gametophytes show abnormal development. Male double-mutant microspore mother cells and female megaspore mother cells undergo meiosis normally. Subsequently, both male and female gametophytes fail at the first post-meiotic, mitotic divisions. Fertile male pollen grains are still formed, although the lack of post-meiotic pollen mitosis I and II leads to fewer Ham1:Ham2 double-mutant pollen grains. Failure of the first post-meiotic, mitotic divisions in the female megagametogenesis, however, results in infertile Ham1:Ham2 double-mutant ovules
additional information
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construction of T-DNA insertion gcn5 mutants, levels of accumulated miRNAs are increased in gcn5-2 mutant compared to the wild-type enzyme, targets of the increased miRNAs are e.g. DCL1 and AGO1, phenotypes, overview
additional information
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generation of two gcn5 alleles, gcn5-1 and gcn5-5. The gcn5 mutants differ significantly from the wild-type during the earliest stages of bud initiation, gcn5-1/hag1-1 and gcn5-5/hag1-5 mutants display overproliferation of young buds and development of abnormal structures around the inflorescence meristem. Gcn5 mutants also display defects in stamen number and arrangement at later stages, phenotypes, overview
additional information
single loss-of-function ham1 mutant displays a wild-type phenotype, while no ham1ham2 double mutant seedling can be recovered, because ham1ham2 double mutation induces severe defects in the formation of male and female gametophyte, resulting in an arrest of mitotic cell cycle at early stages of gametogenesis, phenotypes, overview
additional information
single loss-of-function ham1 mutant displays a wild-type phenotype, while no ham1ham2 double mutant seedling can be recovered, because ham1ham2 double mutation induces severe defects in the formation of male and female gametophyte, resulting in an arrest of mitotic cell cycle at early stages of gametogenesis, phenotypes, overview
additional information
single loss-of-function ham2 mutant displays a wild-type phenotype, while no ham1ham2 double mutant seedling can be recovered, because ham1ham2 double mutation induces severe defects in the formation of male and female gametophyte, resulting in an arrest of mitotic cell cycle at early stages of gametogenesis, phenotypes, overview
additional information
single loss-of-function ham2 mutant displays a wild-type phenotype, while no ham1ham2 double mutant seedling can be recovered, because ham1ham2 double mutation induces severe defects in the formation of male and female gametophyte, resulting in an arrest of mitotic cell cycle at early stages of gametogenesis, phenotypes, overview
additional information
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generation of gcn5 mutant plants which show serious defects in thermotolerance under heat-stress treatment conditions. 5% of the gcn5 seedlings recover when exposed to 38°C for 4 days compared to 55% of the wild-type plants. GCN5 mutation induces extensive changes in gene expression patterns under heat stress, overview. The expression levels of hsp101, HSP90.1, HSP70, HSP70b, HSP70T and genes encoding small heat shock proteins are decreased in the gcn5 mutant. Constitutive UVH6 expression in gcn5 mutant plants partially restores heat tolerance
additional information
generation of mutations that mimic the acetylated and unacetylated forms of the protein, resulting in the inability to acetylate key HBsu lysine residues leading to a more compacted nucleoid
additional information
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generation of mutations that mimic the acetylated and unacetylated forms of the protein, resulting in the inability to acetylate key HBsu lysine residues leading to a more compacted nucleoid
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additional information
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rather than leading to developmental arrest or lethality, RNAi knockdown of Tip60 in Caenorhabditis elegans leads to a recruitment of six instead of three cells into the vulval cell fate, the multivulva phenotype
additional information
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deletion of Rtt109 in the clinical isolate SC5314. rtt109-/- mutant cells lack acetylated H3K56 and are hypersensitive to genotoxic agents. Additionally, rtt109-/- mutant cells constitutively display increased H2A S129 phosphorylation and elevated DNA repair gene expression, consistent with endogenous DNA damage. Importantly, rtt109-/- mutant cells are significantly less pathogenic in BALB/cByJ mice and more susceptible to killing by macrophages in vitro than are wild-type cells, phenotype, overview. rtt109-/- mutant cells display an altered profile of metabolic gene expression compared to the wild-type and constitutively induce DNA repair genes, transcription profile, overview
additional information
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zebrafish homozygous for ENU mutations in the zMoz gene exhibit pharyngeal arch segment identity defects extending to skeletal and nervous system elements of the head. Expression levels of Hox genes in the head region are reduced in zMoz mutants
additional information
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zebrafish homozygous for ENU mutations in the zMoz gene exhibit pharyngeal arch segment identity defects extending to skeletal and nervous system elements of the head. Expression levels of Hox genes in the head region are reduced in zMoz mutants
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additional information
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Both an enok null allele and a point mutation in the zinc finger of the MYST histone acetyltransferase domain cause an arrest in neuroblast proliferation. Enok mutation also results in a slow, but steady decline of egg production over time. However, no difference occurs in the proliferation of wing disk cells. Effects of mutating mof in flies are certainly most pronounced at and most relevant to the male X chromosome. Null mutation of the Hbo1 homologue in Drosophila melanogaster, chameau, leads to lethality at the pupal stage. Haploinsufficiency for chameau leads to defects in position effect variegation, in polycomb group protein mediated repression of homeotic genes and consequent homeotic transformation in thoracic and abdominal segments. Compound heterozygous flies for chameau and the PcG genes polycomb, polyhomeotic, or a mutation in a polycomb response element, Mcp, show more pronounced homeotic transformation than heterozygotes of the PcG genes alone. Depletion of Tip60 by RNAi leads to developmental lethality before or at the early pupal stage
additional information
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MOF levels are strongly diminished after incubating cells for 4 days with interfering RNAs directed against MOF transcript, and are undetectable after 5.5 days
additional information
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loss of HAT1 causes mild growth defects and increases sensitivities to methyl methanesulfonate and camptothecin. Stable expression of tagged Asf1 and C-terminally HA-Flag-tagged histone H4 in enzyme-deficient DT40 HAT-/- cells. Cytosolic Hat1-RbAp48 associate with histones H3 and H4, and Asf1 in vivo
additional information
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mutations that reduce histone acetylation activity also lower the transcriptional activation function of a Gal4-CBP fusion protein in vivo
additional information
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missense mutation within the histone acetyltransferase domain of the TATA binding protein associated factor TAF1 induces ts13 cells to undergo a late G1 arrest and decreases cyclin D1 transcription, construction of several deletion mutants, some of which show slightly reduced activity, while deletion mutants DELTA844-850 and DELTA848-850 are deficient in HAT activity and unable to complement the ts13 defect in cell proliferation and cyclin D1 transcription, hypoacetylation of H3 at the cyclin D1 promoter upon inactivation of TAF1 in ts13 cells, regulation of gene expressions in the pathway, overview
additional information
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down-regulation of the p300 HAT gene by RNAi abrogates the effect of anarcardic acid on TNF-induced NF-kappaB activation. This result shows that p300 HAT is a target of anarcardic acid for supression of NF-kappaB activation
additional information
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a histone acetylase-defective mutant of HBO1 bound at origins is unable to load the MCM complex, also overexpression of the Set8 histone H4 tail-binding domain specifically inhibits MCM loading
additional information
depletion of ATAC2 results in the disassembly of the ATAC complex. Loss of Atac2 leads to reduced histone acetylation, cell death, and G2/M arrest
additional information
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development of a directed evolution protocol that allows the screening of hundreds of histone acetyltransferase mutants, generated by error-prone PCR mutagenesis, for histone acetylating activity, and to identify enhanced thermostability of the human P/CAF histone acetyltransferase. Method development, evaluation, and optimization. Directed evolution results in 24 mutants which show higher thermostability without lowering the catalytic efficiency and substrate specificity, overview. The stabilizing mutations are predominately located at surface of the enzyme
additional information
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overexpression of p300 increases the basal and UV-induced matrix metalloproteinase MMP-1 promoter activity
additional information
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overexpression of the dominant-negative, catalytically inactive mutant Hbo1 causes reduced histone H4 acetylation in both HeLa and MCF-7 cells
additional information
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RNAi depletion of HBO1 in 293-T cells results in an accumulation of cells in S phase of the cell cycle
additional information
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siRNA transfection: down-regulation of Tip60 and DNMT1 by RNA interference, dramatically reduced the levels of acetylated H2AK5
additional information
residue-specific incorporation of ortho-, meta- and para-fluorophenylalanine results in different effects on the selectivity of human histone acetyltransferase protein, PCAF. Varying the position of the fluorine group in the phenylalanine ring confers different effects on the ability of PCAF to acetylate target histone H3 as well as non-histone p53. Incorporation of p-fluorophenylalanine leads to an increase in activity for non-histone p53, while incorporation of m-fluorophenylalanine results in selectivity for histone H3
additional information
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residue-specific incorporation of ortho-, meta- and para-fluorophenylalanine results in different effects on the selectivity of human histone acetyltransferase protein, PCAF. Varying the position of the fluorine group in the phenylalanine ring confers different effects on the ability of PCAF to acetylate target histone H3 as well as non-histone p53. Incorporation of p-fluorophenylalanine leads to an increase in activity for non-histone p53, while incorporation of m-fluorophenylalanine results in selectivity for histone H3
additional information
gene KAT6B mutational screening. shRNA-mediated depletion of KAT6B induces an increase in Rb phosphorylation, and KAT6B shRNA-depleted cells also show diminished expression of Brahma
additional information
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gene KAT6B mutational screening. shRNA-mediated depletion of KAT6B induces an increase in Rb phosphorylation, and KAT6B shRNA-depleted cells also show diminished expression of Brahma
additional information
in vitro-expressed full-length HBO1 exerts less acetylation activity compared to that of the separate MYST domain
additional information
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mutations that reduce histone acetylation activity also lower the transcriptional activation function of a Gal4-CBP fusion protein in vivo
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additional information
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TIP (tension-induced/inhibited) proteins are identified as interacting partners of p300. TIPs do not have intrinsic catalytic activity but they recruit p300 HAT activity. TIP-6 binds directly and indirectly to p300 and histone H4 (H4). Deletion of the SANT domain does not abolish TIP-6 interaction with p300 and H4 but eliminates direct TIP-6 binding to p300. Chromatin immunoprecipitation assays show the recruitment of TIP-6, TIP-6DELTASANT, and p300 to the PPARgamma2 promoter, but H3/H4 acetylation occurres only when p300 is directly associated with TIP-6
additional information
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generation of ATAC2-knockout mice, loss of Atac2 leads to reduced histone acetylation, cell death, and G2/M arrest
additional information
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hematopoietic deficiency in MOZ-DELTAC mice occurs in terms of decreased numbers of blood cells, significantly reduced hematopoietic progenitors and HSC and an increase in nucleated erythrocytes, phenotype, overview. When MOZ-deficient fetal liver cells are transplanted into irradiated mice, recipient mice do not develop a reconstituted hematopoietic system, even when excess numbers of fetal liver cells are transplanted
additional information
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knockdown of PRMT1 by RNAi in erythroid progenitor cells prevents histone acetylation, enhancer and promoter interaction, and recruitment of transcription complexes to the active beta-globin promoter. Restoration of PRMT1 expression in PRMT1 knockout cells rescues erythroid differentiation and beta-globin transcription
additional information
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loss of function of Moz causes defects in the hematopoietic stem cell compartment. Generation of different Moz mutant alleles with similar consequences for the hematopoietic system, phenotypes, overview. Qkf gt/gt mutants that survive to weaning age, which are less than 50% on an inbred 129Sv/Pas background, are smaller than littermate controls, have craniofacial abnormalities, skeletal abnormalities, and a disproportional reduction in the size of the cerebral cortex. Developing Qkf gt/gt mutant forebrain at embryonic day 11.5 contains fewer cerebrocortical progenitor cells, the cerebral cortex primordium, the cortical plate, contains fewer neurons and is reduced in size at embryonic days 13.5, 15.5, and 17.5. Mof mutant mouse embryos arrest in development at the blastocyst stage. RNAi screening in mouse embryonic stem cells reveals that Tip60 is required for pluripotency, and genome-wide expression analysis of Tip60-depleted embryonic stem cells suggests that Tip60 represses a large number of genes that are expressed during differentiation. Tip60 mutant mouse embryos die before implantation
additional information
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neonatal cbp+/- mice are behaviourally impaired and display perturbed vocalization behaviour. Knockdown of CBP by siRNA causes a reduction in betaII-tubulin-positive neurons, and inhibits neurogenesis and gliogenesis, cell phenotype, overview
additional information
contribution of PCAF to post-ischemic neovascularization in a hind limb ischemia model23, using enzyme-deficient PCAF-/- mice, phenotype, overview
additional information
deletion of PCAF, PCAF targeting in wild-type mice impairs inhibits Treg function in vitro and in vivo, phenotype, overview
additional information
deletion of PCAF, PCAF targeting in wild-type mice impairs inhibits Treg function in vitro and in vivo, phenotype, overview
additional information
generation of a strain of T cell-specific Gcn5 knockout (GCN5 KO) mice by breeding Lck-Cre transgenic mice with Gcn5 floxed mice. In these mice, Cre recombinase expression driven by the Lck promoter mediates Gcn5 deletion from the CD4/CD8 double-negative stage. Immunoblot analysis demonstrates that GCN5 is efficiently deleted from thymic T cells. The percentages of cells at CD4/CD8 double-positive and single-positive stages are not altered in the thymus of GCN5 KO mice. But GCN5 gene deletion results in an about 20% reduction in the total thymocyte numbers in mice. As a consequence, a similar level reduction in the absolute numbers of CD4/CD8 double-positive and single-positive cells. While a slight but statistically significant increase in the percentage of double-negative cells is observed upon Gcn5 gene deletion, their absolute number is not altered due to the reduction in total thymocytes in GCN5 KO mice. Ectopic GCN5 expression significantly enhances EGR2 acetylation without affecting total protein expression levels. Gene expression profiles in the GCN5 knockdown DN32, overview
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generation of mKO mice, mice harboring LoxP sites flanking exons 3-19 of the GCN5 gene, referred to as GCN5flox/flox, usage of Cre-LoxP methodology to generate mice with muscle-specific knockout of GCN5 (mKO) and floxed, wildtype littermates. Despite successful knockdown of GCN5 activity in skeletal muscle of mKO mice, whole-body energy expenditure as well as skeletal muscle mitochondrial abundance and maximal respiratory capacity are comparable between mKO and wild-type mice. No differences in skeletal muscle expression of several genes between wild-type and GCN5 mKO mice, overview. Skeletal muscle gene expression of metabolic, angiogenic, and mitochondrial genes is not affected by loss of GCN5. Loss of GCN5 does not alter body composition, in vivo metabolism or energy expenditure
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in vitro-expressed full-length HBO1 exerts less acetylation activity compared to that of the separate MYST domain
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generation of a strain of T cell-specific Gcn5 knockout (GCN5 KO) mice by breeding Lck-Cre transgenic mice with Gcn5 floxed mice. In these mice, Cre recombinase expression driven by the Lck promoter mediates Gcn5 deletion from the CD4/CD8 double-negative stage. Immunoblot analysis demonstrates that GCN5 is efficiently deleted from thymic T cells. The percentages of cells at CD4/CD8 double-positive and single-positive stages are not altered in the thymus of GCN5 KO mice. But GCN5 gene deletion results in an about 20% reduction in the total thymocyte numbers in mice. As a consequence, a similar level reduction in the absolute numbers of CD4/CD8 double-positive and single-positive cells. While a slight but statistically significant increase in the percentage of double-negative cells is observed upon Gcn5 gene deletion, their absolute number is not altered due to the reduction in total thymocytes in GCN5 KO mice. Ectopic GCN5 expression significantly enhances EGR2 acetylation without affecting total protein expression levels. Gene expression profiles in the GCN5 knockdown DN32, overview
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a chimera comprising the PfGCN5 histone acetyltransferase domain fused to the remainder of yeast GCN5 fully rescues the yGCB5 mutant. The histone acyltransferase domains in PfGCN5 and yGCN5 are interchangeable
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a chimera comprising the PfGCN5 histone acetyltransferase domain fused to the remainder of yeast GCN5 fully rescues the yGCB5 mutant. The histone acyltransferase domains in PfGCN5 and yGCN5 are interchangeable
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recombinant protein expressed in prokaryotes and insect cells does not show activity, recombinant protein purified from the parasites exhibits a predilection to acetylate histone H4 in vitro at K5, K8, K12 and K16
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recombinant protein expressed in prokaryotes and insect cells does not show activity, recombinant protein purified from the parasites exhibits a predilection to acetylate histone H4 in vitro at K5, K8, K12 and K16
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temperature sensitive Esa1 mutant strain shows reduced activity in vitro and needs histone H4 acetylated at Lys5 as substrate in vivo
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comparison of enzyme activity and cell growth in wild-type and hat1-deficient cells, overview
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deletion of either ASF1 or RTT109 in cycling cells ablates H3-K56 acetylation and leads to elevated levels of DNA damage-associated gammaH2A and Rad53 phopshorylation
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double mutant esa1/gcn5 at 36°C is very sensitive to 6-azauracil (inhibitor impeding elongation by lowering nucleotide pools) and shows littler but still strong effect at 30°C (permissive temperature), gene length dependent defects in transcription
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effects of sas2 mutation in yeast are quite specific to the euchromatin/heterochromatin boundary
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gcn5 deletion mutant (reduced H3 acetylation) at 36°C (restrictive temperature) is very sensitive to 6-azauracil (inhibitor impeding elongation by lowering nucleotide pools) but shows less effect at 30°C (permissive temperature), gene length dependent defects in transcription
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mutant cells lacking RTT109 have a high level of CAG/CTG repeat contractions and a twofold increase in breakage at CAG/CTG repeats. Dnl4 and Rad51-dependent pathways do play a role in creating some of the repeat contractions in rtt109-deficient cells
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wild-type, mutants of core stress-granule (SG) subunits pbp1DELTA and pub1DELTA, along with NuA4 non-essential mutants eaf1DELTA and eaf7DELTA, are transformed with a Pab1-GFP expressing plasmid. None of the mutants examined display a significant increase or constitutive formation of SGs under glucose conditions compared to wild-type. Upon glucose deprivation (GD), Pab1-GFP SGs are induced in wild-type cells but the induction is significantly reduced in pub1DELTA and pbp1DELTA cells. Upon glucose deprivation eaf1DELTA and eaf7DELTA cells show a decrease in Pab1-GFP SGs to a similar extent as pbp1DELTA and pub1DELTA cells. Decreases in GD-SG formation are seen for NuA4 mutants' eaf3DELTA and eaf5DELTA. Furthermore, while the temperature-sensitive allele of ESA1, esa1-L254P (esa1-ts) form GD-SGs at the permissive temperature (25°C), when pre-incubated at the non-permissive temperature (37°C) prior to 10 minutes of glucose deprivation, there is a significant decrease in Pab1-GFP foci formation, indicating that the catalytic activity of NuA4 is required for Pab1-GFP SG formation. While gcn5DELTA cells do not display a significant reduction in GD-SG assembly compared to wild-type cells using the endogenously integrated Pab1-GFP, eaf7DELTAgcn5DELTA cells display a significant reduction in GD-SG formation at 10 minutes compared to both wild-type and single KAT mutants
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wild-type, mutants of core stress-granule (SG) subunits pbp1DELTA and pub1DELTA, along with NuA4 non-essential mutants eaf1DELTA and eaf7DELTA, are transformed with a Pab1-GFP expressing plasmid. None of the mutants examined display a significant increase or constitutive formation of SGs under glucose conditions compared to wild-type. Upon glucose deprivation (GD), Pab1-GFP SGs are induced in wild-type cells but the induction is significantly reduced in pub1DELTA and pbp1DELTA cells. Upon glucose deprivation eaf1DELTA and eaf7DELTA cells show a decrease in Pab1-GFP SGs to a similar extent as pbp1DELTA and pub1DELTA cells. Decreases in GD-SG formation are seen for NuA4 mutants' eaf3DELTA and eaf5DELTA. Furthermore, while the temperature-sensitive allele of ESA1, esa1-L254P (esa1-ts) form GD-SGs at the permissive temperature (25°C), when pre-incubated at the non-permissive temperature (37°C) prior to 10 minutes of glucose deprivation, there is a significant decrease in Pab1-GFP foci formation, indicating that the catalytic activity of NuA4 is required for Pab1-GFP SG formation. While gcn5DELTA cells do not display a significant reduction in GD-SG assembly compared to wild-type cells using the endogenously integrated Pab1-GFP, eaf7DELTAgcn5DELTA cells display a significant reduction in GD-SG formation at 10 minutes compared to both wild-type and single KAT mutants
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mutant cells lacking RTT109 have a high level of CAG/CTG repeat contractions and a twofold increase in breakage at CAG/CTG repeats. Dnl4 and Rad51-dependent pathways do play a role in creating some of the repeat contractions in rtt109-deficient cells
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wild-type, mutants of core stress-granule (SG) subunits pbp1DELTA and pub1DELTA, along with NuA4 non-essential mutants eaf1DELTA and eaf7DELTA, are transformed with a Pab1-GFP expressing plasmid. None of the mutants examined display a significant increase or constitutive formation of SGs under glucose conditions compared to wild-type. Upon glucose deprivation (GD), Pab1-GFP SGs are induced in wild-type cells but the induction is significantly reduced in pub1DELTA and pbp1DELTA cells. Upon glucose deprivation eaf1DELTA and eaf7DELTA cells show a decrease in Pab1-GFP SGs to a similar extent as pbp1DELTA and pub1DELTA cells. Decreases in GD-SG formation are seen for NuA4 mutants' eaf3DELTA and eaf5DELTA. Furthermore, while the temperature-sensitive allele of ESA1, esa1-L254P (esa1-ts) form GD-SGs at the permissive temperature (25°C), when pre-incubated at the non-permissive temperature (37°C) prior to 10 minutes of glucose deprivation, there is a significant decrease in Pab1-GFP foci formation, indicating that the catalytic activity of NuA4 is required for Pab1-GFP SG formation. While gcn5DELTA cells do not display a significant reduction in GD-SG assembly compared to wild-type cells using the endogenously integrated Pab1-GFP, eaf7DELTAgcn5DELTA cells display a significant reduction in GD-SG formation at 10 minutes compared to both wild-type and single KAT mutants
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deletion of the hat1 gene from Schizosaccharomyces pombe causes increased sensitivity to the DNA-damaging agent methyl methanesulfonate in the absence of any additional mutations
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deletion of the hat1 gene from Schizosaccharomyces pombe causes increased sensitivity to the DNA-damaging agent methyl methanesulfonate in the absence of any additional mutations
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isolation of a temperature-sensitive allele of the essential mst gene. Mutant mst1 cells show a pleiotropic phenotype at the restrictive temperature. They are sensitive to a variety of DNA-damaging agents and to the spindle poison thiabendazole. Mutant mst1 has an increased frequency of Rad22 repair foci, suggesting endogenous damage, overview
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recombinant enzyme containing fluorinated Phe analogues shows reduced half-life: 27.5 min for the recombinant p-fluorophenylalanine-substituted tGCN5, 5.4 min for recombinant m-fluorophenylalanine-substituted tGCN5, and 6.8 min for recombinant o-fluorophenylalanine-substituted tGCN5
