Top2a

Summary

Gene Symbol: Top2a
Description: topoisomerase (DNA) II alpha
Alias: Top-2, DNA topoisomerase 2-alpha, DNA Topoisomerase II alpha, DNA topoisomerase II, alpha isozyme
Species: mouse
Products:     Top2a

Top Publications

  1. St Pierre J, Wright D, Rowe T, Wright S. DNA topoisomerase II is essential for preimplantation mouse development. Mol Reprod Dev. 2002;61:347-57 pubmed
    ..In addition, topo IIalpha is newly synthesized at the 2-cell stage. These results establish an essential function for topo II in mouse preimplantation embryonic development. ..
  2. Capranico G, Tinelli S, Austin C, Fisher M, Zunino F. Different patterns of gene expression of topoisomerase II isoforms in differentiated tissues during murine development. Biochim Biophys Acta. 1992;1132:43-8 pubmed
    The expression of DNA topoisomerase II alpha and beta genes was studied in murine normal tissues...
  3. Dawlaty M, Malureanu L, Jeganathan K, Kao E, Sustmann C, Tahk S, et al. Resolution of sister centromeres requires RanBP2-mediated SUMOylation of topoisomerase IIalpha. Cell. 2008;133:103-15 pubmed publisher
    ..Furthermore, mice with low amounts of RanBP2 are highly sensitive to tumor formation. Together, these data identify RanBP2 as a chromosomal instability gene that regulates Topo IIalpha by sumoylation and suppresses tumorigenesis. ..
  4. St Pierre J, Wright D, Rowe T, Wright S. DNA topoisomerase II distribution in mouse preimplantation embryos. Mol Reprod Dev. 2002;61:335-46 pubmed
    ..The different immunofluorescent staining patterns indicate topo IIalpha and beta may serve different roles during the embryonic cell cycle. ..
  5. Adachi N, Kobayashi M, Koyama H. Cell cycle-dependent regulation of the mouse DNA topoisomerase IIalpha gene promoter. Biochem Biophys Res Commun. 1997;230:105-9 pubmed
    ..We found that the topo IIalpha gene promoter has the cell cycle-dependent activity, which is low in G1, rises in S, and peaks in G2/M. We suggest that the level of topo IIalpha mRNA is determined by the cell cycle-regulated promoter. ..
  6. Azarova A, Lyu Y, Lin C, Tsai Y, Lau J, Wang J, et al. Roles of DNA topoisomerase II isozymes in chemotherapy and secondary malignancies. Proc Natl Acad Sci U S A. 2007;104:11014-9 pubmed
    ..These results point to the importance of developing Top2alpha-specific anticancer drugs for effective chemotherapy without the development of treatment-related secondary malignancies. ..
  7. Wyles S, Yamada S, Oommen S, Maleszewski J, Beraldi R, Martinez Fernandez A, et al. Inhibition of DNA topoisomerase II selectively reduces the threat of tumorigenicity following induced pluripotent stem cell-based myocardial therapy. Stem Cells Dev. 2014;23:2274-82 pubmed publisher
  8. Houlard M, Godwin J, Metson J, Lee J, Hirano T, Nasmyth K. Condensin confers the longitudinal rigidity of chromosomes. Nat Cell Biol. 2015;17:771-81 pubmed publisher
    ..Pre-assembled meiotic bivalents unravel when condensin is inactivated by TEV cleavage, proving that it actually holds chromatin fibres together. ..
  9. Gómez Herreros F, Romero Granados R, Zeng Z, Alvarez Quilón A, Quintero C, Ju L, et al. TDP2-dependent non-homologous end-joining protects against topoisomerase II-induced DNA breaks and genome instability in cells and in vivo. PLoS Genet. 2013;9:e1003226 pubmed publisher

More Information

Publications55

  1. Kawanami K, Nakamura T, Ono M, Kusano T, Okada K, Kikuchi A, et al. Decreased DNA topoisomerase II alpha expression and cold-sensitive growth in a mouse mammary cancer cell line resistant to etoposide and doxorubicin. Oncol Res. 1996;8:197-206 pubmed
    ..Decreased topo II alpha expression might have led to the acquisition of drug resistance to etoposide in FM3A/VP-2B, and appeared to be linked with the cold-sensitive growth. We also present a corrected mouse topo II alpha cDNA sequence. ..
  2. Akimitsu N, Kamura K, Tone S, Sakaguchi A, Kikuchi A, Hamamoto H, et al. Induction of apoptosis by depletion of DNA topoisomerase IIalpha in mammalian cells. Biochem Biophys Res Commun. 2003;307:301-7 pubmed
    ..Our results suggest that topo IIalpha-depleted cells with the droplet-like nuclear structure induce apoptosis, which is dependent on caspase and p53 activity during the G1 phase in mammalian cells. ..
  3. Hwang G, Sun F, O Brien M, Eppig J, Handel M, Jordan P. SMC5/6 is required for the formation of segregation-competent bivalent chromosomes during meiosis I in mouse oocytes. Development. 2017;144:1648-1660 pubmed publisher
  4. Pett L, Kiakos K, Satam V, Patil P, Laughlin Toth S, Gregory M, et al. Modulation of topoisomerase II? expression and chemosensitivity through targeted inhibition of NF-Y:DNA binding by a diamino p-anisyl-benzimidazole (Hx) polyamide. Biochim Biophys Acta Gene Regul Mech. 2017;1860:617-629 pubmed publisher
    ..This article is part of a Special Issue entitled: Nuclear Factor Y in Development and Disease, edited by Prof. Roberto Mantovani. ..
  5. Solovyan V, Bezvenyuk Z, Salminen A, Austin C, Courtney M. The role of topoisomerase II in the excision of DNA loop domains during apoptosis. J Biol Chem. 2002;277:21458-67 pubmed
  6. Kang X, Song C, Du X, Zhang C, Liu Y, Liang L, et al. PTEN stabilizes TOP2A and regulates the DNA decatenation. Sci Rep. 2015;5:17873 pubmed publisher
    ..We show that PTEN is physically associated with a decatenation enzyme TOP2A and that PTEN influences its stability through OTUD3 deubiquitinase...
  7. Juenke J, Holden J. The distribution of DNA topoisomerase II isoforms in differentiated adult mouse tissues. Biochim Biophys Acta. 1993;1216:191-6 pubmed
    ..The beta isoform is also abundant in spleen and in addition is present in kidney and liver. Type II topoisomerase is low in brain and heart. These results suggest different functions for these two isoforms of DNA topoisomerase II. ..
  8. Adachi N, Miyaike M, Ikeda H, Kikuchi A. Characterization of cDNA encoding the mouse DNA topoisomerase II that can complement the budding yeast top2 mutation. Nucleic Acids Res. 1992;20:5297-303 pubmed
    ..The functional expression of the mouse DNA topoisomerase II in yeast was further confirmed by enzymatic assays and by immunological methods with antibodies specific for the mouse enzyme. ..
  9. Li X, Yu C, Wang Z, Zhang Y, Liu X, Zhou D, et al. DNA topoisomerase II is dispensable for oocyte meiotic resumption but is essential for meiotic chromosome condensation and separation in mice. Biol Reprod. 2013;89:118 pubmed publisher
    ..These results indicated that TOP2 had a specific, crucial function in meiosis I. Thus, we identified important functions of TOP2 during oocyte maturation and provided novel insights into the decatenation checkpoint during meiosis. ..
  10. Deffie A, Bosman D, Goldenberg G. Evidence for a mutant allele of the gene for DNA topoisomerase II in adriamycin-resistant P388 murine leukemia cells. Cancer Res. 1989;49:6879-82 pubmed
    ..6-kilobase mRNA. The unique 5.5-kilobase mRNA in resistant cells may represent a shortened transcript of the mutated topoisomerase II allele. ..
  11. Escargueil A, Plisov S, Filhol O, Cochet C, Larsen A. Mitotic phosphorylation of DNA topoisomerase II alpha by protein kinase CK2 creates the MPM-2 phosphoepitope on Ser-1469. J Biol Chem. 2000;275:34710-8 pubmed
    b>DNA topoisomerase II alpha is required for chromatin condensation during prophase...
  12. Squire J, McPherson J, Beatty B, Goldenberg G. Allelic fusion of DNA topoisomerase II alpha and retinoic acid receptor alpha genes in adriamycin-resistant p388 murine leukemia revealed by fluorescence in situ hybridization. Cytogenet Cell Genet. 1996;75:164-6 pubmed
    ..ADR)-sensitive and ADR-resistant murine cells demonstrated a close juxtaposition of topoisomerase II alpha (Top2a) and retinoic acid receptor alpha (Rara) genes in adjacent chromatin in the drug-resistant cells, and a close but ..
  13. Emanuelli A, Borroni A, Apel Sarid L, Shah P, Ayyathan D, Koganti P, et al. Smurf2-Mediated Stabilization of DNA Topoisomerase IIα Controls Genomic Integrity. Cancer Res. 2017;77:4217-4227 pubmed publisher
    ..Our results identified Smurf2 as an essential regulator of Topo IIα, providing novel insights into its control and into the suggested tumor-suppressor functions of Smurf2. Cancer Res; 77(16); 4217-27. ©2017 AACR. ..
  14. Kobayashi M, Adachi N, Koyama H. Characterization of the 3' untranslated region of mouse DNA topoisomerase IIalpha mRNA. Gene. 1998;215:329-37 pubmed
    ..Our results strongly suggest that the mouse topoisomerase IIalpha 3' UTR by itself is not involved in the cell-cycle-dependent mRNA stability. ..
  15. Miller E, Hargreaves D, Kadoch C, Chang C, Calarco J, Hodges C, et al. TOP2 synergizes with BAF chromatin remodeling for both resolution and formation of facultative heterochromatin. Nat Struct Mol Biol. 2017;24:344-352 pubmed publisher
  16. Storbeck M, Hupperich K, Gaspar J, Meganathan K, Mart nez Carrera L, Wirth R, et al. Neuronal-specific deficiency of the splicing factor Tra2b causes apoptosis in neurogenic areas of the developing mouse brain. PLoS ONE. 2014;9:e89020 pubmed publisher
    ..Apoptotic events triggered via p21 might not be restricted to the developing brain but could possibly be generalized to the whole organism and explain early embryonic lethality in Tra2b-depleted mice...
  17. Adachi N, Ikeda H, Kikuchi A. Mutant isolation of mouse DNA topoisomerase II alpha in yeast. Nucleic Acids Res. 1994;22:4229-33 pubmed
    ..Therefore we have isolated the first conditional mutation in the mouse TOP2 alpha. ..
  18. Solovyan V. Characterization of apoptotic pathway associated with caspase-independent excision of DNA loop domains. Exp Cell Res. 2007;313:1347-60 pubmed
    ..Our results suggest that caspase-independent excision of chromatin loop domains represents a separate cell death pathway, which operates either in parallel or independently from caspase-dependent internucleosomal DNA fragmentation. ..
  19. Onda T, Toyoda E, Miyazaki O, Seno C, Kagaya S, Okamoto K, et al. NK314, a novel topoisomerase II inhibitor, induces rapid DNA double-strand breaks and exhibits superior antitumor effects against tumors resistant to other topoisomerase II inhibitors. Cancer Lett. 2008;259:99-110 pubmed
    ..As a result of this unique mechanism of DNA breakage, NK314 showed substantial growth inhibition of topoisomerase II inhibitor-resistant tumors. ..
  20. Dykhuizen E, Hargreaves D, Miller E, Cui K, Korshunov A, Kool M, et al. BAF complexes facilitate decatenation of DNA by topoisomerase II?. Nature. 2013;497:624-7 pubmed publisher
    ..Endogenous BAF complexes interact directly with endogenous topoisomerase II? (TOP2A) through BAF250a and are required for the binding of TOP2A to approximately 12,000 sites across the genome...
  21. Thakurela S, Garding A, Jung J, Schübeler D, Burger L, Tiwari V. Gene regulation and priming by topoisomerase II? in embryonic stem cells. Nat Commun. 2013;4:2478 pubmed publisher
    ..These findings suggest that topoisomerase II? not only contributes to stem-cell transcriptome regulation but also primes developmental genes for subsequent activation upon differentiation. ..
  22. McPherson J, Brown G, Goldenberg G. Characterization of a DNA topoisomerase IIalpha gene rearrangement in adriamycin-resistant P388 leukemia: expression of a fusion messenger RNA transcript encoding topoisomerase IIalpha and the retinoic acid receptor alpha locus. Cancer Res. 1993;53:5885-9 pubmed
    ..of Adriamycin-sensitive and -resistant P388 murine leukemia cells have suggested that a reduction in DNA topoisomerase II alpha (topo II alpha) enzyme activity and protein levels in drug-resistant cell lines (A. M. Deffie, J. K...
  23. Zhang L, Jiang M, Shui Y, Chen Y, Wang Q, Hu W, et al. DNA topoisomerase II inhibitors induce macrophage ABCA1 expression and cholesterol efflux-an LXR-dependent mechanism. Biochim Biophys Acta. 2013;1831:1134-45 pubmed publisher
    ..Our study also describes a new function for Topo II inhibitors in addition to their role in anti-tumorigenesis...
  24. Kingsmore S, Tang C, Lo C, Hui C, Hwang J, Seldin M. Genetic mapping of the mouse topoisomerase II alpha gene to chromosome 11. Mamm Genome. 1993;4:288-9 pubmed
  25. Leduc F, Maquennehan V, Nkoma G, Boissonneault G. DNA damage response during chromatin remodeling in elongating spermatids of mice. Biol Reprod. 2008;78:324-32 pubmed
    ..Because this process is part of the normal developmental program of the spermatids, dramatic consequences for the genomic integrity of the developing male gamete may arise should any alteration in the process occur. ..
  26. Shapiro P, Whalen A, Tolwinski N, Wilsbacher J, Froelich Ammon S, Garcia M, et al. Extracellular signal-regulated kinase activates topoisomerase IIalpha through a mechanism independent of phosphorylation. Mol Cell Biol. 1999;19:3551-60 pubmed
  27. Gowher H, Brick K, Camerini Otero R, Felsenfeld G. Vezf1 protein binding sites genome-wide are associated with pausing of elongating RNA polymerase II. Proc Natl Acad Sci U S A. 2012;109:2370-5 pubmed publisher
    ..We further show that Vezf1 interacts with Mrg15/Mrgbp, a protein that recognizes H3K36 trimethylation, consistent with the role of histone modifications at alternatively spliced sites. ..
  28. Mann M, Pereira E, Liao N, Hendershot L. UPR-induced resistance to etoposide is downstream of PERK and independent of changes in topoisomerase II? levels. PLoS ONE. 2012;7:e47931 pubmed publisher
  29. Shafee N, Smith C, Wei S, Kim Y, Mills G, Hortobagyi G, et al. Cancer stem cells contribute to cisplatin resistance in Brca1/p53-mediated mouse mammary tumors. Cancer Res. 2008;68:3243-50 pubmed publisher
    ..b>Top2A expression is also down-regulated in secondary drug-resistant tumor populations and, in one case, was accompanied ..
  30. Cobb J, Reddy R, Park C, Handel M. Analysis of expression and function of topoisomerase I and II during meiosis in male mice. Mol Reprod Dev. 1997;46:489-98 pubmed
    ..These studies constitute evidence for a functional requirement for topoisomerase II activity in the transition from meiotic prophase to meiotic metaphase I in mammalian spermatocytes. ..
  31. Le N, Sielaff A, Cooper A, Mackay H, Brown T, Kotecha M, et al. Binding of f-PIP, a pyrrole- and imidazole-containing triamide, to the inverted CCAAT box-2 of the topoisomerase IIalpha promoter and modulation of gene expression in cells. Bioorg Med Chem Lett. 2006;16:6161-4 pubmed
    ..The results suggested that the triamide was able to enter the nucleus, interacted with the target site within ICB2, inhibited NF-Y binding, and activated gene expression. ..
  32. Yoshida K, Yamaguchi T, Shinagawa H, Taira N, Nakayama K, Miki Y. Protein kinase C delta activates topoisomerase IIalpha to induce apoptotic cell death in response to DNA damage. Mol Cell Biol. 2006;26:3414-31 pubmed
    ..These findings indicate that PKCdelta regulates topoisomerase IIalpha and thereby cell fate in the genotoxic stress response. ..
  33. Ogawa Y, Kawano Y, Yamazaki Y, Onishi Y. Shikonin shortens the circadian period: possible involvement of Top2 inhibition. Biochem Biophys Res Commun. 2014;443:339-43 pubmed publisher
    ..b>Top2a siRNA also shortened period length, suggesting that Top2 is involved in this process...
  34. Heinonen J, Zhang F, Surmann Schmitt C, Honkala S, Stock M, Poutanen M, et al. Defects in chondrocyte maturation and secondary ossification in mouse knee joint epiphyses due to Snorc deficiency. Osteoarthritis Cartilage. 2017;25:1132-1142 pubmed publisher
    ..The interaction identified between recombinant Snorc core protein and FGF2 suggest functions related to FGF signaling. ..
  35. Baloch Z, Cohen S, Fresa K, Coffman F. Modulation of topoisomerase activities by tumor necrosis factor. Cell Immunol. 1995;160:98-103 pubmed
    ..However, neither TNF cytotoxicity nor the enhancement of TNF cytotoxicity by topoisomerase inhibitors appears to require the TNF-mediated increases in topoisomerase activities. ..
  36. Samata K, Yamagishi T, Ichihara T, Nanaumi K, Ikeda T, Ikeya H, et al. Establishment and characterization of a mouse FM3A cell mutant resistant to topoisomerase II-inhibitor NC-190. Cancer Chemother Pharmacol. 2002;50:367-72 pubmed
    ..These results indicate that the NC-190-resistant cell line FM/NC-R contains a mutated DNA topoisomerase IIalpha. ..
  37. Jacobsen R, Mazloumi Gavgani F, Mellgren G, Lewis A. DNA Topoisomerase II? contributes to the early steps of adipogenesis in 3T3-L1 cells. Cell Signal. 2016;28:1593-603 pubmed publisher
    ..Considering that Topoisomerases II are targets in cancer chemotherapy, our results highlight that treatment of cancer with Topo II inhibitors may alter metabolic processes in the adipose tissue. ..
  38. Ura K, Hirose S. Possible role of DNA topoisomerase II on transcription of the homeobox gene Hox-2.1 in F9 embryonal carcinoma cells. Nucleic Acids Res. 1991;19:6087-92 pubmed
    ..1 mRNA after blocking transcription by actinomycin D show that etoposide does not affect stability of the mRNA. These observations indicate that DNA topoisomerase II is involved in the control of Hox-2.1 gene transcription. ..
  39. Lu L, Kuang H, Korakavi G, Yu X. Topoisomerase II regulates the maintenance of DNA methylation. J Biol Chem. 2015;290:851-60 pubmed publisher
    ..Inhibiting this activity impairs DNA methylation at multiple genomic loci. We have uncovered a novel mechanism during the maintenance of DNA methylation. ..
  40. Hu Q, Bhattacharya C, Maity S. CCAAT binding factor (CBF) binding mediates cell cycle activation of topoisomerase IIalpha. Conventional CBF activation domains are not required. J Biol Chem. 2002;277:37191-200 pubmed
  41. Park J, Kim H, Park M, Kim C, Chung Y, Hong Y, et al. Topoisomerase II alpha as a universal tumor antigen: antitumor immunity in murine tumor models and H-2K(b)-restricted T cell epitope. Cancer Immunol Immunother. 2010;59:747-57 pubmed publisher
    ..Based on these data, Top2alpha is suggested to be a universal target for cancer immunotherapy. ..
  42. Adachi N, Miyaike M, Kato S, Kanamaru R, Koyama H, Kikuchi A. Cellular distribution of mammalian DNA topoisomerase II is determined by its catalytically dispensable C-terminal domain. Nucleic Acids Res. 1997;25:3135-42 pubmed
  43. Sapetto Rebow B, McLoughlin S, O Shea L, O Leary O, Willer J, Alvarez Y, et al. Maternal topoisomerase II alpha, not topoisomerase II beta, enables embryonic development of zebrafish top2a-/- mutants. BMC Dev Biol. 2011;11:71 pubmed publisher
    Genetic alterations in human topoisomerase II alpha (TOP2A) are linked to cancer susceptibility...
  44. Xiao H, Goodrich D. The retinoblastoma tumor suppressor protein is required for efficient processing and repair of trapped topoisomerase II-DNA-cleavable complexes. Oncogene. 2005;24:8105-13 pubmed
    ..The functional status of pRb, therefore, may influence sensitivity to etoposide by facilitating the repair of trapped TOP2-DNA complexes as well as by enforcing cell cycle checkpoints. ..
  45. Gómez R, Viera A, Berenguer I, Llano E, Pendas A, Barbero J, et al. Cohesin removal precedes topoisomerase II?-dependent decatenation at centromeres in male mammalian meiosis II. Chromosoma. 2014;123:129-46 pubmed publisher
    ..We suggest that the cohesin removal is a prerequisite for the posterior topoisomerase II?-mediated resolution of persisting catenations between segregating chromatids during anaphase II. ..
  46. Lee J, Ogushi S, Saitou M, Hirano T. Condensins I and II are essential for construction of bivalent chromosomes in mouse oocytes. Mol Biol Cell. 2011;22:3465-77 pubmed publisher