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Literature summary for 5.6.2.2 extracted from
- DNA topoisomerase II and its growing repertoire of biological functions (2009), Nat. Rev. Cancer, 9, 327-337.
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | cells depleted of Top2 can complete replication, but not chromosome decatenation, and lose viability at mitosis, Top2 depeletion phenotype, overview | Homo sapiens |
| additional information | cells depleted of Top2 can complete replication, but not chromosome decatenation, and lose viability at mitosis, Top2 depeletion phenotype, overview | Saccharomyces cerevisiae |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| etoposide | inhibits the religation step and traps Top2 as a covalent complex with the enzyme covalently bound to DNA with broken DNA strands | Homo sapiens |  |
| ICRF-187 | - |
Homo sapiens | |
| ICRF-187 | - |
Saccharomyces cerevisiae | |
| ICRF-193 | - |
Homo sapiens | |
| ICRF-193 | - |
Saccharomyces cerevisiae | |
| mAMSA | inhibits the religation step and traps Top2 as a covalent complex with the enzyme covalently bound to DNA with broken DNA strands | Homo sapiens | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| nucleus | - |
Homo sapiens | 5634 | - |
| nucleus | - |
Saccharomyces cerevisiae | 5634 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | Homo sapiens | the enzyme introduces transient double strand breaks to alter DNA topology, generation of a transient double strand break, with each subunit breaking one DNA strand. The mechanism of DNA cleavage provides several distinct advantages including the protection of DNA ends and the ability to quickly and efficiently religate the DNA strand break. The positively supercoiled DNA at the replication fork can isomerize by migration of the positive supercoiling into wrapping of the two replicated strands. This structure called a precatenane, is a substrate for Top2 mediated DNA catenation, and may represent a plausible mechanism for Top2 action during replication elongation | ? | - |
? | |
| additional information | Saccharomyces cerevisiae | the enzyme introduces transient double strand breaks to alter DNA topology, generation of a transient double strand break, with each subunit breaking one DNA strand. The mechanism of DNA cleavage provides several distinct advantages including the protection of DNA ends and the ability to quickly and efficiently religate the DNA strand break. The positively supercoiled DNA at the replication fork can isomerize by migration of the positive supercoiling into wrapping of the two replicated strands. This structure called a precatenane, is a substrate for Top2 mediated DNA catenation, and may represent a plausible mechanism for Top2 action during replication elongation | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Saccharomyces cerevisiae | - |
- |
- |
Reaction
| Reaction | Comment | Organism | Reaction ID |
|---|---|---|---|
| ATP-dependent breakage, passage and rejoining of double-stranded DNA | reaction mechanism, overview | Homo sapiens | |
| ATP-dependent breakage, passage and rejoining of double-stranded DNA | reaction mechanism, overview | Saccharomyces cerevisiae |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| carcinoma cell | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | the enzyme introduces transient double strand breaks to alter DNA topology, generation of a transient double strand break, with each subunit breaking one DNA strand. The mechanism of DNA cleavage provides several distinct advantages including the protection of DNA ends and the ability to quickly and efficiently religate the DNA strand break. The positively supercoiled DNA at the replication fork can isomerize by migration of the positive supercoiling into wrapping of the two replicated strands. This structure called a precatenane, is a substrate for Top2 mediated DNA catenation, and may represent a plausible mechanism for Top2 action during replication elongation | Homo sapiens | ? | - |
? | |
| additional information | the enzyme introduces transient double strand breaks to alter DNA topology, generation of a transient double strand break, with each subunit breaking one DNA strand. The mechanism of DNA cleavage provides several distinct advantages including the protection of DNA ends and the ability to quickly and efficiently religate the DNA strand break. The positively supercoiled DNA at the replication fork can isomerize by migration of the positive supercoiling into wrapping of the two replicated strands. This structure called a precatenane, is a substrate for Top2 mediated DNA catenation, and may represent a plausible mechanism for Top2 action during replication elongation | Saccharomyces cerevisiae | ? | - |
? | |
| additional information | reaction mechanism, DNA cleavage by Top2 uses a tyrosine that is activated to attack the phosphodiester backbone of DNA and form a phosphotyrosine linkage, overview | Saccharomyces cerevisiae | ? | - |
? | |
| additional information | reaction mechanism, DNA cleavage by Top2 uses a tyrosine that is activated to attack the phosphodiester backbone of DNA and form a phosphotyrosine linkage. Topological changes in DNA require the introduction of DNA strand breaks, and topoisomerases provide a safe mechanism for introducing these changes, overview | Homo sapiens | ? | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| homodimer | domain structure and fucntions, overview | Homo sapiens |
| homodimer | domain structure and fucntions, overview | Saccharomyces cerevisiae |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| DNA topoisomerase II | - |
Homo sapiens |
| DNA topoisomerase II | - |
Saccharomyces cerevisiae |
| Top2 | - |
Homo sapiens |
| Top2 | - |
Saccharomyces cerevisiae |
| type II topoisomerase | - |
Homo sapiens |
| type II topoisomerase | - |
Saccharomyces cerevisiae |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | the N-terminal domain of the protein carries the ATP binding domain consisting of a GHKL fold | Homo sapiens | |
| ATP | the N-terminal domain of the protein carries the ATP binding domain consisting of a GHKL fold | Saccharomyces cerevisiae | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | topoisomerase II poisons generate DNA damage, in addition to inhibition of enzyme activity, and cause delay of cell cycle progression due to DNA damage checkpoints | Homo sapiens |
| malfunction | topoisomerase II poisons generate DNA damage, in addition to inhibition of enzyme activity, and cause delay of cell cycle progression due to DNA damage checkpoints | Saccharomyces cerevisiae |
| physiological function | Top2 functions, such as DNA replication, transcription and chromosome segregation, are processes that are essential for preventing tumorigenesis. Top2 plays a key role in chromosome structure and chromosome condensation | Homo sapiens |
| physiological function | Top2 functions, such as DNA replication, transcription and chromosome segregation, are processes that are essential for preventing tumorigenesis. Top2 plays a key role in chromosome structure and chromosome condensation | Saccharomyces cerevisiae |
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