TOP2A explained

DNA topoisomerase IIα is a human enzyme encoded by the TOP2A gene.

Topoisomerase IIα relieves 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. 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] P53,^[8] and TOPBP1.^[9]

In other species

In Drosophila Hadlaczky et al 1988 found DNA topoisomerase II α to correlate with cell proliferation - but β did not.^[10]

See also

• Topoisomerase II
• TOP2B - Topoisomerase II beta
• Gene duplication
• Ataxia-telangiectasia
• TOPBP1

Further reading

• Watt PM, Hickson ID . Structure and function of type II DNA topoisomerases . The Biochemical Journal . 303 . Pt 3 . 681–695 . November 1994 . 7980433 . 1137600 . 10.1042/bj3030681 .
• Bronner C, Hopfner R, Mousli M . Transcriptional regulation of the human topoisomerase IIalpha gene . Anticancer Research . 22 . 2A . 605–612 . 2002 . 12014628 .
• Järvinen TA, Liu ET . Topoisomerase IIalpha gene (TOP2A) amplification and deletion in cancer--more common than anticipated . Cytopathology . 14 . 6 . 309–313 . December 2003 . 14632727 . 10.1046/j.0956-5507.2003.00105.x . 29586255 .

Notes and References

1. Deweese. J. E.. Osheroff. N.. 2009-02-01. The DNA cleavage reaction of topoisomerase II: wolf in sheep's clothing. Nucleic Acids Research. en. 37. 3. 738–748. 10.1093/nar/gkn937. 0305-1048. 2647315. 19042970.
2. Web site: Entrez Gene: TOP2A topoisomerase (DNA) II alpha 170kDa.
3. Emanuelli A, Borroni AP, Apel-Sarid L, Shah PA, Ayyathan DM, Koganti P, Levy-Cohen G, Blank M . 6 . Smurf2-Mediated Stabilization of DNA Topoisomerase IIα Controls Genomic Integrity . Cancer Research . 77 . 16 . 4217–4227 . August 2017 . 28611047 . 10.1158/0008-5472.CAN-16-2828 . free .
4. Tsai SC, Valkov N, Yang WM, Gump J, Sullivan D, Seto E . Histone deacetylase interacts directly with DNA topoisomerase II . Nature Genetics . 26 . 3 . 349–353 . November 2000 . 11062478 . 10.1038/81671 . 19301396 .
5. Johnson CA, Padget K, Austin CA, Turner BM . Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis . The Journal of Biological Chemistry . 276 . 7 . 4539–4542 . February 2001 . 11136718 . 10.1074/jbc.C000824200 . free .
6. Ajuh P, Kuster B, Panov K, Zomerdijk JC, Mann M, Lamond AI . Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry . The EMBO Journal . 19 . 23 . 6569–6581 . December 2000 . 11101529 . 305846 . 10.1093/emboj/19.23.6569 .
7. Leroy Liu . Mao Y, Desai SD, Liu LF . SUMO-1 conjugation to human DNA topoisomerase II isozymes . The Journal of Biological Chemistry . 275 . 34 . 26066–26073 . August 2000 . 10862613 . 10.1074/jbc.M001831200 . free .
8. Cowell IG, Okorokov AL, Cutts SA, Padget K, Bell M, Milner J, Austin CA . Human topoisomerase IIalpha and IIbeta interact with the C-terminal region of p53 . Experimental Cell Research . 255 . 1 . 86–94 . February 2000 . 10666337 . 10.1006/excr.1999.4772 .
9. Broderick . Ronan . Niedzwiedz . Wojciech . 2015-08-12 . Sister chromatid decatenation: bridging the gaps in our knowledge . Cell Cycle . 14 . 19 . 3040–3044 . 10.1080/15384101.2015.1078039 . 1538-4101 . 4825568 . 26266709.
10. Wang JC . DNA topoisomerases . Annual Review of Biochemistry . 65 . 1 . 635–692 . 1996 . 8811192 . 10.1146/annurev.bi.65.070196.003223 . .