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, beta, is localized to chromosome 3 and the alpha form is localized to chromosome 17. The gene encoding this enzyme functions as the target for several anticancer agents, for example mitoxantrone, 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. Alternative splicing of this gene results in two transcript variants; however, the second variant has not yet been fully described.[3]
↑Tan KB, Dorman TE, Falls KM, Chung TD, Mirabelli CK, Crooke ST, Mao J (Jan 1992). "Topoisomerase II alpha and topoisomerase II beta genes: characterization and mapping to human chromosomes 17 and 3, respectively". Cancer Research. 52 (1): 231–4. PMID1309226.
↑Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D, Ogawa S, Unno K, Okubo M, Tokita A, Nakagawa T, Ito T, Ishimi Y, Nagasawa H, Matsumoto T, Yanagisawa J, Kato S (Jun 2003). "The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome". Cell. 113 (7): 905–17. doi:10.1016/s0092-8674(03)00436-7. PMID12837248.
↑ 5.05.1Tsai SC, Valkov N, Yang WM, Gump J, Sullivan D, Seto E (Nov 2000). "Histone deacetylase interacts directly with DNA topoisomerase II". Nature Genetics. 26 (3): 349–53. doi:10.1038/81671. PMID11062478.
↑Johnson CA, Padget K, Austin CA, Turner BM (Feb 2001). "Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis". The Journal of Biological Chemistry. 276 (7): 4539–42. doi:10.1074/jbc.C000824200. PMID11136718.
↑Cowell IG, Okorokov AL, Cutts SA, Padget K, Bell M, Milner J, Austin CA (Feb 2000). "Human topoisomerase IIalpha and IIbeta interact with the C-terminal region of p53". Experimental Cell Research. 255 (1): 86–94. doi:10.1006/excr.1999.4772. PMID10666337.
↑Mao Y, Desai SD, Liu LF (Aug 2000). "SUMO-1 conjugation to human DNA topoisomerase II isozymes". The Journal of Biological Chemistry. 275 (34): 26066–73. doi:10.1074/jbc.M001831200. PMID10862613.
↑Nakano H, Yamazaki T, Miyatake S, Nozaki N, Kikuchi A, Saito T (Mar 1996). "Specific interaction of topoisomerase II beta and the CD3 epsilon chain of the T cell receptor complex". The Journal of Biological Chemistry. 271 (11): 6483–9. doi:10.1074/jbc.271.11.6483. PMID8626450.
Austin CA, Fisher LM (Jun 1990). "Isolation and characterization of a human cDNA clone encoding a novel DNA topoisomerase II homologue from HeLa cells". FEBS Letters. 266 (1–2): 115–7. doi:10.1016/0014-5793(90)81520-X. PMID2163884.
Austin CA, Sng JH, Patel S, Fisher LM (Mar 1993). "Novel HeLa topoisomerase II is the II beta isoform: complete coding sequence and homology with other type II topoisomerases". Biochimica et Biophysica Acta. 1172 (3): 283–91. doi:10.1016/0167-4781(93)90215-Y. PMID8383537.
Nakano H, Yamazaki T, Miyatake S, Nozaki N, Kikuchi A, Saito T (Mar 1996). "Specific interaction of topoisomerase II beta and the CD3 epsilon chain of the T cell receptor complex". The Journal of Biological Chemistry. 271 (11): 6483–9. doi:10.1074/jbc.271.11.6483. PMID8626450.
Ng SW, Liu Y, Schnipper LE (Dec 1997). "Cloning and characterization of the 5'-flanking sequence for the human DNA topoisomerase II beta gene". Gene. 203 (2): 113–9. doi:10.1016/S0378-1119(97)00500-3. PMID9426241.
Yamane K, Kawabata M, Tsuruo T (Dec 1997). "A DNA-topoisomerase-II-binding protein with eight repeating regions similar to DNA-repair enzymes and to a cell-cycle regulator". European Journal of Biochemistry / FEBS. 250 (3): 794–9. doi:10.1111/j.1432-1033.1997.00794.x. PMID9461304.
Cowell IG, Willmore E, Chalton D, Marsh KL, Jazrawi E, Fisher LM, Austin CA (Sep 1998). "Nuclear distribution of human DNA topoisomerase IIbeta: a nuclear targeting signal resides in the 116-residue C-terminal tail". Experimental Cell Research. 243 (2): 232–40. doi:10.1006/excr.1998.4150. PMID9743583.
Lang AJ, Mirski SE, Cummings HJ, Yu Q, Gerlach JH, Cole SP (Oct 1998). "Structural organization of the human TOP2A and TOP2B genes". Gene. 221 (2): 255–66. doi:10.1016/S0378-1119(98)00468-5. PMID9795238.
Sng JH, Heaton VJ, Bell M, Maini P, Austin CA, Fisher LM (Mar 1999). "Molecular cloning and characterization of the human topoisomerase IIalpha and IIbeta genes: evidence for isoform evolution through gene duplication". Biochimica et Biophysica Acta. 1444 (3): 395–406. doi:10.1016/S0167-4781(99)00020-2. PMID10095062.
Bjergbaek L, Jensen S, Westergaard O, Andersen AH (Sep 1999). "Using a biochemical approach to identify the primary dimerization regions in human DNA topoisomerase IIalpha". The Journal of Biological Chemistry. 274 (37): 26529–36. doi:10.1074/jbc.274.37.26529. PMID10473615.
Cowell IG, Okorokov AL, Cutts SA, Padget K, Bell M, Milner J, Austin CA (Feb 2000). "Human topoisomerase IIalpha and IIbeta interact with the C-terminal region of p53". Experimental Cell Research. 255 (1): 86–94. doi:10.1006/excr.1999.4772. PMID10666337.
Mao Y, Desai SD, Liu LF (Aug 2000). "SUMO-1 conjugation to human DNA topoisomerase II isozymes". The Journal of Biological Chemistry. 275 (34): 26066–73. doi:10.1074/jbc.M001831200. PMID10862613.
Mirski SE, Voskoglou-Nomikos T, Young LC, Deeley RG, Campling BG, Gerlach JH, Cole SP (Jun 2000). "Simultaneous quantitation of topoisomerase II alpha and beta isoform mRNAs in lung tumor cells and normal and malignant lung tissue". Laboratory Investigation. 80 (6): 787–95. doi:10.1038/labinvest.3780083. PMID10879730.