TOP2A

{{Short description|Protein-coding gene in the species Homo sapiens}}

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{{Cite journal|last1=Deweese|first1=J. E.|last2=Osheroff|first2=N.|date=2009-02-01|title=The DNA cleavage reaction of topoisomerase II: wolf in sheep's clothing|journal=Nucleic Acids Research|language=en|volume=37|issue=3|pages=738–748|doi=10.1093/nar/gkn937|issn=0305-1048|pmc=2647315|pmid=19042970}} and a variety of mutations in this gene have been associated with the development of drug resistance.{{Citation needed|date=December 2021}} Reduced activity of this enzyme may also play a role in ataxia-telangiectasia.{{cite web | title = Entrez Gene: TOP2A topoisomerase (DNA) II alpha 170kDa| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7153}}

Interactions

TOP2A has been shown to interact with SMURF2,{{cite journal | vauthors = Emanuelli A, Borroni AP, Apel-Sarid L, Shah PA, Ayyathan DM, Koganti P, Levy-Cohen G, Blank M | display-authors = 6 | title = Smurf2-Mediated Stabilization of DNA Topoisomerase IIα Controls Genomic Integrity | journal = Cancer Research | volume = 77 | issue = 16 | pages = 4217–4227 | date = August 2017 | pmid = 28611047 | doi = 10.1158/0008-5472.CAN-16-2828 | doi-access = free | url = https://aacr.figshare.com/ndownloader/files/39860088 }} HDAC1,{{cite journal | vauthors = Tsai SC, Valkov N, Yang WM, Gump J, Sullivan D, Seto E | title = Histone deacetylase interacts directly with DNA topoisomerase II | journal = Nature Genetics | volume = 26 | issue = 3 | pages = 349–353 | date = November 2000 | pmid = 11062478 | doi = 10.1038/81671 | s2cid = 19301396 }}{{cite journal | vauthors = Johnson CA, Padget K, Austin CA, Turner BM | title = Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis | journal = The Journal of Biological Chemistry | volume = 276 | issue = 7 | pages = 4539–4542 | date = February 2001 | pmid = 11136718 | doi = 10.1074/jbc.C000824200 | doi-access = free }} CDC5L,{{cite journal | vauthors = Ajuh P, Kuster B, Panov K, Zomerdijk JC, Mann M, Lamond AI | title = Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry | journal = The EMBO Journal | volume = 19 | issue = 23 | pages = 6569–6581 | date = December 2000 | pmid = 11101529 | pmc = 305846 | doi = 10.1093/emboj/19.23.6569 }} Small ubiquitin-related modifier 1,{{cite journal|author3-link=Leroy Liu | vauthors = Mao Y, Desai SD, Liu LF | title = SUMO-1 conjugation to human DNA topoisomerase II isozymes | journal = The Journal of Biological Chemistry | volume = 275 | issue = 34 | pages = 26066–26073 | date = August 2000 | pmid = 10862613 | doi = 10.1074/jbc.M001831200 | doi-access = free }} P53,{{cite journal | vauthors = Cowell IG, Okorokov AL, Cutts SA, Padget K, Bell M, Milner J, Austin CA | title = Human topoisomerase IIalpha and IIbeta interact with the C-terminal region of p53 | journal = Experimental Cell Research | volume = 255 | issue = 1 | pages = 86–94 | date = February 2000 | pmid = 10666337 | doi = 10.1006/excr.1999.4772 }} and TOPBP1.{{Cite journal |last1=Broderick |first1=Ronan |last2=Niedzwiedz |first2=Wojciech |date=2015-08-12 |title=Sister chromatid decatenation: bridging the gaps in our knowledge |journal=Cell Cycle |volume=14 |issue=19 |pages=3040–3044 |doi=10.1080/15384101.2015.1078039 |issn=1538-4101 |pmc=4825568 |pmid=26266709}}

In other species

In Drosophila Hadlaczky et al 1988 found DNA topoisomerase II α to correlate with cell proliferation - but β did not.{{cite journal | vauthors = Wang JC | title = DNA topoisomerases | journal = Annual Review of Biochemistry | volume = 65 | issue = 1 | pages = 635–692 | year = 1996 | pmid = 8811192 | doi = 10.1146/annurev.bi.65.070196.003223 | publisher = Annual Reviews }}

TOP2A

Interactions

In other species

See also

References

Further reading