TOP2A
DNA topoisomerase 2-alpha is an enzyme that in humans is encoded by the TOP2A gene.
This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This nuclear enzyme is involved in processes such as chromosome condensation, chromatid separation, and the relief of torsional stress that occurs during DNA transcription and replication. It catalyzes the transient breaking and rejoining of two strands of duplex DNA which allows the strands to pass through one another, thus altering the topology of DNA. Two forms of this enzyme exist as likely products of a gene duplication event. The gene encoding this form, alpha, is localized to chromosome 17 and the beta gene is localized to chromosome 3. The gene encoding this enzyme functions as the target for several anticancer agents and a variety of mutations in this gene have been associated with the development of drug resistance. Reduced activity of this enzyme may also play a role in ataxia-telangiectasia.[5]
Interactions
TOP2A has been shown to interact with HDAC1,[6][7] CDC5L,[8] Small ubiquitin-related modifier 1[9] and P53.[10]
See also
- Topoisomerase II
- TOP2B - Topoisomerase II beta
- Gene duplication
- Ataxia-telangiectasia
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000131747 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020914 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: TOP2A topoisomerase (DNA) II alpha 170kDa".
- ^ Tsai, S C; Valkov N; Yang W M; Gump J; Sullivan D; Seto E (November 2000). "Histone deacetylase interacts directly with DNA topoisomerase II". Nat. Genet. 26 (3). UNITED STATES: 349–53. doi:10.1038/81671. ISSN 1061-4036. PMID 11062478.
- ^ Johnson, C A; Padget K; Austin C A; Turner B M (February 2001). "Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis". J. Biol. Chem. 276 (7). United States: 4539–42. doi:10.1074/jbc.C000824200. ISSN 0021-9258. PMID 11136718.
- ^ Ajuh, P; Kuster B; Panov K; Zomerdijk J C; Mann M; Lamond A I (Dec 2000). "Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry". EMBO J. 19 (23). ENGLAND: 6569–81. doi:10.1093/emboj/19.23.6569. ISSN 0261-4189. PMC 305846. PMID 11101529.
- ^ Mao, Y; Desai S D; Liu L F (August 2000). "SUMO-1 conjugation to human DNA topoisomerase II isozymes". J. Biol. Chem. 275 (34). UNITED STATES: 26066–73. doi:10.1074/jbc.M001831200. ISSN 0021-9258. PMID 10862613.
- ^ Cowell, I G; Okorokov A L; Cutts S A; Padget K; Bell M; Milner J; Austin C A (February 2000). "Human topoisomerase IIalpha and IIbeta interact with the C-terminal region of p53". Exp. Cell Res. 255 (1). UNITED STATES: 86–94. doi:10.1006/excr.1999.4772. ISSN 0014-4827. PMID 10666337.
Further reading
- Watt PM, Hickson ID (1994). "Structure and function of type II DNA topoisomerases". Biochem. J. 303 (3): 681–95. PMC 1137600. PMID 7980433.
- Bronner C, Hopfner R, Mousli M (2002). "Transcriptional regulation of the human topoisomerase IIalpha gene". Anticancer Res. 22 (2A): 605–12. PMID 12014628.
- Järvinen TA, Liu ET (2004). "Topoisomerase IIalpha gene (TOP2A) amplification and deletion in cancer--more common than anticipated". Cytopathology. 14 (6): 309–13. doi:10.1046/j.0956-5507.2003.00105.x. PMID 14632727.
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