Biology:TOP2A
 Generic protein structure example |
DNA topoisomerase IIα is a human enzyme encoded by the TOP2A gene.
Topoisomerase IIα relives topological DNA stress during transcription, condenses chromosomes, and separates chromatids. It catalyzes the transient breaking and rejoining of two strands of duplex DNA which allows the strands to pass through one another. 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 chemotherapy agents[1] and a variety of mutations in this gene have been associated with the development of drug resistance.[citation needed] Reduced activity of this enzyme may also play a role in ataxia-telangiectasia.[2]
Interactions
TOP2A has been shown to interact with SMURF2,[3] HDAC1,[4][5] CDC5L,[6] Small ubiquitin-related modifier 1[7] and P53.[8]
In other species
In Drosophila Hadlaczky et al 1988 found DNA topoisomerase II α to correlate with cell proliferation - but β did not.[9]
See also
- Topoisomerase II
- TOP2B - Topoisomerase II beta
- Gene duplication
- Ataxia-telangiectasia
References
- ↑ Deweese, J. E.; Osheroff, N. (2009-02-01). "The DNA cleavage reaction of topoisomerase II: wolf in sheep's clothing" (in en). Nucleic Acids Research 37 (3): 738–748. doi:10.1093/nar/gkn937. ISSN 0305-1048. PMID 19042970.
- ↑ "Entrez Gene: TOP2A topoisomerase (DNA) II alpha 170kDa". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7153.
- ↑ "Smurf2-Mediated Stabilization of DNA Topoisomerase IIα Controls Genomic Integrity". Cancer Research 77 (16): 4217–4227. August 2017. doi:10.1158/0008-5472.CAN-16-2828. PMID 28611047.
- ↑ "Histone deacetylase interacts directly with DNA topoisomerase II". Nature Genetics 26 (3): 349–353. November 2000. doi:10.1038/81671. PMID 11062478.
- ↑ "Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis". The Journal of Biological Chemistry 276 (7): 4539–4542. February 2001. doi:10.1074/jbc.C000824200. PMID 11136718.
- ↑ "Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry". The EMBO Journal 19 (23): 6569–6581. December 2000. doi:10.1093/emboj/19.23.6569. PMID 11101529.
- ↑ "SUMO-1 conjugation to human DNA topoisomerase II isozymes". The Journal of Biological Chemistry 275 (34): 26066–26073. August 2000. doi:10.1074/jbc.M001831200. PMID 10862613.
- ↑ "Human topoisomerase IIalpha and IIbeta interact with the C-terminal region of p53". Experimental Cell Research 255 (1): 86–94. February 2000. doi:10.1006/excr.1999.4772. PMID 10666337.
- ↑ "DNA topoisomerases". Annual Review of Biochemistry (Annual Reviews) 65 (1): 635–692. 1996. doi:10.1146/annurev.bi.65.070196.003223. PMID 8811192.
Further reading
- "Structure and function of type II DNA topoisomerases". The Biochemical Journal 303 (Pt 3): 681–695. November 1994. doi:10.1042/bj3030681. PMID 7980433.
- "Transcriptional regulation of the human topoisomerase IIalpha gene". Anticancer Research 22 (2A): 605–612. 2002. PMID 12014628.
- "Topoisomerase IIalpha gene (TOP2A) amplification and deletion in cancer--more common than anticipated". Cytopathology 14 (6): 309–313. December 2003. doi:10.1046/j.0956-5507.2003.00105.x. PMID 14632727.
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