| Standard Name | TOP2 1 |
|---|---|
| Systematic Name | YNL088W |
| Alias | TOR3 , TRF3 2 |
| Feature Type | ORF, Verified |
| Description | Topoisomerase II, relieves torsional strain in DNA by cleaving and re-sealing the phosphodiester backbone of both positively and negatively supercoiled DNA; cleaves complementary strands; localizes to axial cores in meiosis; required for replication slow zone (RSZ) breakage following Mec1p inactivation (3, 4, 5, 6, 7 and see Summary Paragraph) |
| Name Description | TOPoisomerase 1, 8 |
| Chromosomal Location | |
|---|---|
| Genetic position: -70 cM |
| View Computational GO annotations for TOP2 | |
| Molecular Function | |
| Manually curated | |
| Biological Process | |
| Manually curated |
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| Cellular Component | |
| Manually curated | |
| High-throughput |
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| Classical genetics | |
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| overexpression | |
| reduction of function |
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| Large-scale survey | |
| null | |
| overexpression | |
| reduction of function | |
| Resources |
| 102 total interaction(s) for 71 unique genes/features. | |
| Physical Interactions |
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| Genetic Interactions |
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| Resources |
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| Resources |
| Localization | |
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| Phosphorylation | PhosphoGRID | PhosphoPep Database |
| Structure | |
| Homologs |
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| Genetic position: -70 cM | |||||||||||||
| Last Update | Coordinates: 2011-02-03 | Sequence: 1996-07-31 | ||||||||||||
| Subfeature details |
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| Retrieve sequences | |||||||||||||
| S288C only | |
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| S288C vs. other species | |
| S288C vs. other strains |
| External Links | All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB |
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| Primary SGDID | S000005032 |
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Topoisomerases catalyze the interconversion between topological states of DNA by breaking and rejoining DNA strands. These changes in DNA topology are required during several cellular processes such as replication, transcription, recombination, and chromosome condensation (9). There are three classes of topoisomerases that are distinguished by substrate (IA, IB, II). Type I topoisomerases cleave one DNA strand, while Type II enzymes cleave a pair of complementary DNA strands (5). The type IB topoisomerases relax both positively and negatively supercoiled DNA; Top2p is a highly conserved, essential protein with homologs in C. elegans, Drosophila, and humans (12); detailed comparisons between yeast and human Top2p have been done (13). Top2p, like other type II enzymes, hydrolyzes ATP and cleaves a pair of complementary strands to relax both positive and negative supercoils in DNA (9). To maintain the integrity of the cleaved DNA, Top2p forms a transient bridge that spans across the double-strand DNA break (5). Several antitumor drugs target Top2p (14). There are inhibitors that block Top2 catalytic activity as well as Top2p poisons that stabilize Top2-DNA complexes.
| 1) | Holm C, et al. (1985) DNA topoisomerase II is required at the time of mitosis in yeast. Cell 41(2):553-63 |
| 2) | Sadoff BU, et al. (1995) Isolation of mutants of Saccharomyces cerevisiae requiring DNA topoisomerase I. Genetics 141(2):465-79 |
| 3) | Klein F, et al. (1992) Localization of RAP1 and topoisomerase II in nuclei and meiotic chromosomes of yeast. J Cell Biol 117(5):935-48 |
| 4) | Goto T and Wang JC (1984) Yeast DNA topoisomerase II is encoded by a single-copy, essential gene. Cell 36(4):1073-80 |
| 5) | Wang JC (1996) DNA topoisomerases. Annu Rev Biochem 65:635-92 |
| 6) | Roca J (1995) The mechanisms of DNA topoisomerases. Trends Biochem Sci 20(4):156-60 |
| 7) | Hashash N, et al. (2012) Topoisomerase II- and Condensin-Dependent Breakage of MEC1(ATR)-Sensitive Fragile Sites Occurs Independently of Spindle Tension, Anaphase, or Cytokinesis. PLoS Genet 8(10):e1002978 |
| 8) | DiNardo S, et al. (1984) DNA topoisomerase II mutant of Saccharomyces cerevisiae: topoisomerase II is required for segregation of daughter molecules at the termination of DNA replication. Proc Natl Acad Sci U S A 81(9):2616-20 |
| 9) | Berger JM (1998) Structure of DNA topoisomerases. Biochim Biophys Acta 1400(1-3):3-18 |
| 10) | Thrash C, et al. (1985) Cloning, characterization, and sequence of the yeast DNA topoisomerase I gene. Proc Natl Acad Sci U S A 82(13):4374-8 |
| 11) | Goto T and Wang JC (1985) Cloning of yeast TOP1, the gene encoding DNA topoisomerase I, and construction of mutants defective in both DNA topoisomerase I and DNA topoisomerase II. Proc Natl Acad Sci U S A 82(21):7178-82 |
| 12) | Hodges PE, et al. (1999) The Yeast Proteome Database (YPD): a model for the organization and presentation of genome-wide functional data. Nucleic Acids Res 27(1):69-73 |
| 13) | Strumberg D, et al. (1999) Molecular analysis of yeast and human type II topoisomerases. Enzyme-DNA and drug interactions. J Biol Chem 274(40):28246-55 |
| 14) | Beck WT, et al. (1993) Drug resistance associated with altered DNA topoisomerase II. Adv Enzyme Regul 33():113-27 |





