DNA topoisomerase 2-alpha

NameDNA topoisomerase 2-alpha
Synonyms
  • 5.99.1.3
  • DNA topoisomerase II, alpha isozyme
  • TOP2
Gene NameTOP2A
OrganismHuman
Amino acid sequence
>lcl|BSEQ0001480|DNA topoisomerase 2-alpha
MEVSPLQPVNENMQVNKIKKNEDAKKRLSVERIYQKKTQLEHILLRPDTYIGSVELVTQQ
MWVYDEDVGINYREVTFVPGLYKIFDEILVNAADNKQRDPKMSCIRVTIDPENNLISIWN
NGKGIPVVEHKVEKMYVPALIFGQLLTSSNYDDDEKKVTGGRNGYGAKLCNIFSTKFTVE
TASREYKKMFKQTWMDNMGRAGEMELKPFNGEDYTCITFQPDLSKFKMQSLDKDIVALMV
RRAYDIAGSTKDVKVFLNGNKLPVKGFRSYVDMYLKDKLDETGNSLKVIHEQVNHRWEVC
LTMSEKGFQQISFVNSIATSKGGRHVDYVADQIVTKLVDVVKKKNKGGVAVKAHQVKNHM
WIFVNALIENPTFDSQTKENMTLQPKSFGSTCQLSEKFIKAAIGCGIVESILNWVKFKAQ
VQLNKKCSAVKHNRIKGIPKLDDANDAGGRNSTECTLILTEGDSAKTLAVSGLGVVGRDK
YGVFPLRGKILNVREASHKQIMENAEINNIIKIVGLQYKKNYEDEDSLKTLRYGKIMIMT
DQDQDGSHIKGLLINFIHHNWPSLLRHRFLEEFITPIVKVSKNKQEMAFYSLPEFEEWKS
STPNHKKWKVKYYKGLGTSTSKEAKEYFADMKRHRIQFKYSGPEDDAAISLAFSKKQIDD
RKEWLTNFMEDRRQRKLLGLPEDYLYGQTTTYLTYNDFINKELILFSNSDNERSIPSMVD
GLKPGQRKVLFTCFKRNDKREVKVAQLAGSVAEMSSYHHGEMSLMMTIINLAQNFVGSNN
LNLLQPIGQFGTRLHGGKDSASPRYIFTMLSSLARLLFPPKDDHTLKFLYDDNQRVEPEW
YIPIIPMVLINGAEGIGTGWSCKIPNFDVREIVNNIRRLMDGEEPLPMLPSYKNFKGTIE
ELAPNQYVISGEVAILNSTTIEISELPVRTWTQTYKEQVLEPMLNGTEKTPPLITDYREY
HTDTTVKFVVKMTEEKLAEAERVGLHKVFKLQTSLTCNSMVLFDHVGCLKKYDTVLDILR
DFFELRLKYYGLRKEWLLGMLGAESAKLNNQARFILEKIDGKIIIENKPKKELIKVLIQR
GYDSDPVKAWKEAQQKVPDEEENEESDNEKETEKSDSVTDSGPTFNYLLDMPLWYLTKEK
KDELCRLRNEKEQELDTLKRKSPSDLWKEDLATFIEELEAVEAKEKQDEQVGLPGKGGKA
KGKKTQMAEVLPSPRGQRVIPRITIEMKAEAEKKNKKKIKNENTEGSPQEDGVELEGLKQ
RLEKKQKREPGTKTKKQTTLAFKPIKKGKKRNPWSDSESDRSSDESNFDVPPRETEPRRA
ATKTKFTMDLDSDEDFSDFDEKTDDEDFVPSDASPPKTKTSPKLSNKELKPQKSVVSDLE
ADDVKGSVPLSSSPPATHFPDETEITNPVPKKNVTVKKTAAKSQSSTSTTGAKKRAAPKG
TKRDPALNSGVSQKPDPAKTKNRRKRKPSTSDDSDSNFEKIVSKAVTSKKSKGESDDFHM
DFDSAVAPRAKSVRAKKPIKYLEESDEDDLF
Number of residues1531
Molecular Weight174383.88
Theoretical pI9.17
GO Classification
Functions
  • DNA binding
  • protein kinase C binding
  • chromatin binding
  • poly(A) RNA binding
  • DNA-dependent ATPase activity
  • DNA topoisomerase type II (ATP-hydrolyzing) activity
  • magnesium ion binding
  • enzyme binding
  • ubiquitin binding
  • protein homodimerization activity
  • protein C-terminus binding
  • histone deacetylase binding
  • drug binding
  • DNA binding, bending
  • protein heterodimerization activity
  • ATP binding
Processes
  • mitotic cell cycle
  • DNA unwinding involved in DNA replication
  • DNA topological change
  • apoptotic chromosome condensation
  • DNA ligation
  • mitotic DNA integrity checkpoint
  • positive regulation of single stranded viral RNA replication via double stranded DNA intermediate
  • resolution of meiotic recombination intermediates
  • regulation of circadian rhythm
  • rhythmic process
  • chromosome segregation
  • positive regulation of viral genome replication
  • mitotic recombination
  • hematopoietic progenitor cell differentiation
  • cellular response to DNA damage stimulus
  • embryonic cleavage
  • positive regulation of apoptotic process
  • positive regulation of transcription from RNA polymerase II promoter
  • sister chromatid segregation
Components
  • DNA topoisomerase complex (ATP-hydrolyzing)
  • nucleus
  • nucleolus
  • nucleoplasm
  • condensed chromosome
  • cytoplasm
  • protein complex
General FunctionUbiquitin binding
Specific FunctionControl of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID292830
UniProtKB IDP11388
UniProtKB Entry NameTOP2A_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0019005|DNA topoisomerase 2-alpha (TOP2A)
ATGGAAGTGTCACCATTGCAGCCTGTAAATGAAAATATGCAAGTCAACAAAATAAAGAAA
AATGAAGATGCTAAGAAAAGACTGTCTGTTGAAAGAATCTATCAAAAGAAAACACAATTG
GAACATATTTTGCTCCGCCCAGACACCTACATTGGTTCTGTGGAATTAGTGACCCAGCAA
ATGTGGGTTTACGATGAAGATGTTGGCATTAACTATAGGGAAGTCACTTTTGTTCCTGGT
TTGTACAAAATCTTTGATGAGATTCTAGTTAATGCTGCGGACAACAAACAAAGGGACCCA
AAAATGTCTTGTATTAGAGTCACAATTGATCCGGAAAACAATTTAATTAGTATATGGAAT
AATGGAAAAGGTATTCCTGTTGTTGAACACAAAGTTGAAAAGATGTATGTCCCAGCTCTC
ATATTTGGACAGCTCCTAACTTCTAGTAACTATGATGATGATGAAAAGAAAGTGACAGGT
GGTCGAAATGGCTATGGAGCCAAATTGTGTAACATATTCAGTACCAAATTTACTGTGGAA
ACAGCCAGTAGAGAATACAAGAAAATGTTCAAACAGACATGGATGGATAATATGGGAAGA
GCTGGTGAGATGGAACTCAAGCCCTTCAATGGAGAAGATTATACATGTATCACCTTTCAG
CCTGATTTGTCTAAGTTTAAAATGCAAAGCCTGGACAAAGATATTGTTGCACTAATGGTC
AGAAGAGCATATGATATTGCTGGATCCACCAAAGATGTCAAAGTCTTTCTTAATGGAAAT
AAACTGCCAGTAAAAGGATTTCGTAGTTATGTGGACATGTATTTGAAGGACAAGTTGGAT
GAAACTGGTAACTCCTTGAAAGTAATACATGAACAAGTAAACCACAGGTGGGAAGTGTGT
TTAACTATGAGTGAAAAAGGCTTTCAGCAAATTAGCTTTGTCAACAGCATTGCTACATCC
AAGGGTGGCAGACATGTTGATTATGTAGCTGATCAGATTGTGACTAAACTTGTTGATGTT
GTGAAGAAGAAGAACAAGGGTGGTGTTGCAGTAAAAGCACATCAGGTGAAAAATCACATG
TGGATTTTTGTAAATGCCTTAATTGAAAACCCAACCTTTGACTCTCAGACAAAAGAAAAC
ATGACTTTACAACCCAAGAGCTTTGGATCAACATGCCAATTGAGTGAAAAATTTATCAAA
GCTGCCATTGGCTGTGGTATTGTAGAAAGCATACTAAACTGGGTGAAGTTTAAGGCCCAA
GTCCAGTTAAACAAGAAGTGTTCAGCTGTAAAACATAATAGAATCAAGGGAATTCCCAAA
CTCGATGATGCCAATGATGCAGGGGGCCGAAACTCCACTGAGTGTACGCTTATCCTGACT
GAGGGAGATTCAGCCAAAACTTTGGCTGTTTCAGGCCTTGGTGTGGTTGGGAGAGACAAA
TATGGGGTTTTCCCTCTTAGAGGAAAAATACTCAATGTTCGAGAAGCTTCTCATAAGCAG
ATCATGGAAAATGCTGAGATTAACAATATCATCAAGATTGTGGGTCTTCAGTACAAGAAA
AACTATGAAGATGAAGATTCATTGAAGACGCTTCGTTATGGGAAGATAATGATTATGACA
GATCAGGACCAAGATGGTTCCCACATCAAAGGCTTGCTGATTAATTTTATCCATCACAAC
TGGCCCTCTCTTCTGCGACATCGTTTTCTGGAGGAATTTATCACTCCCATTGTAAAGGTA
TCTAAAAACAAGCAAGAAATGGCATTTTACAGCCTTCCTGAATTTGAAGAGTGGAAGAGT
TCTACTCCAAATCATAAAAAATGGAAAGTCAAATATTACAAAGGTTTGGGCACCAGCACA
TCAAAGGAAGCTAAAGAATACTTTGCAGATATGAAAAGACATCGTATCCAGTTCAAATAT
TCTGGTCCTGAAGATGATGCTGCTATCAGCCTGGCCTTTAGCAAAAAACAGATAGATGAT
CGAAAGGAATGGTTAACTAATTTCATGGAGGATAGAAGACAACGAAAGTTACTTGGGCTT
CCTGAGGATTACTTGTATGGACAAACTACCACATATCTGACATATAATGACTTCATCAAC
AAGGAACTTATCTTGTTCTCAAATTCTGATAACGAGAGATCTATCCCTTCTATGGTGGAT
GGTTTGAAACCAGGTCAGAGAAAGGTTTTGTTTACTTGCTTCAAACGGAATGACAAGCGA
GAAGTAAAGGTTGCCCAATTAGCTGGATCAGTGGCTGAAATGTCTTCTTATCATCATGGT
GAGATGTCACTAATGATGACCATTATCAATTTGGCTCAGAATTTTGTGGGTAGCAATAAT
CTAAACCTCTTGCAGCCCATTGGTCAGTTTGGTACCAGGCTACATGGTGGCAAGGATTCT
GCTAGTCCACGATACATCTTTACAATGCTCAGCTCTTTGGCTCGATTGTTATTTCCACCA
AAAGATGATCACACGTTGAAGTTTTTATATGATGACAACCAGCGTGTTGAGCCTGAATGG
TACATTCCTATTATTCCCATGGTGCTGATAAATGGTGCTGAAGGAATCGGTACTGGGTGG
TCCTGCAAAATCCCCAACTTTGATGTGCGTGAAATTGTAAATAACATCAGGCGTTTGATG
GATGGAGAAGAACCTTTGCCAATGCTTCCAAGTTACAAGAACTTCAAGGGTACTATTGAA
GAACTGGCTCCAAATCAATATGTGATTAGTGGTGAAGTAGCTATTCTTAATTCTACAACC
ATTGAAATCTCAGAGCTTCCCGTCAGAACATGGACCCAGACATACAAAGAACAAGTTCTA
GAACCCATGTTGAATGGCACCGAGAAGACACCTCCTCTCATAACAGACTATAGGGAATAC
CATACAGATACCACTGTGAAATTTGTTGTGAAGATGACTGAAGAAAAACTGGCAGAGGCA
GAGAGAGTTGGACTACACAAAGTCTTCAAACTCCAAACTAGTCTCACATGCAACTCTATG
GTGCTTTTTGACCACGTAGGCTGTTTAAAGAAATATGACACGGTGTTGGATATTCTAAGA
GACTTTTTTGAACTCAGACTTAAATATTATGGATTAAGAAAAGAATGGCTCCTAGGAATG
CTTGGTGCTGAATCTGCTAAACTGAATAATCAGGCTCGCTTTATCTTAGAGAAAATAGAT
GGCAAAATAATCATTGAAAATAAGCCTAAGAAAGAATTAATTAAAGTTCTGATTCAGAGG
GGATATGATTCGGATCCTGTGAAGGCCTGGAAAGAAGCCCAGCAAAAGGTTCCAGATGAA
GAAGAAAATGAAGAGAGTGACAACGAAAAGGAAACTGAAAAGAGTGACTCCGTAACAGAT
TCTGGACCAACCTTCAACTATCTTCTTGATATGCCCCTTTGGTATTTAACCAAGGAAAAG
AAAGATGAACTCTGCAGGCTAAGAAATGAAAAAGAACAAGAGCTGGACACATTAAAAAGA
AAGAGTCCATCAGATTTGTGGAAAGAAGACTTGGCTACATTTATTGAAGAATTGGAGGCT
GTTGAAGCCAAGGAAAAACAAGATGAACAAGTCGGACTTCCTGGGAAAGGGGGGAAGGCC
AAGGGGAAAAAAACACAAATGGCTGAAGTTTTGCCTTCTCCGCGTGGTCAAAGAGTCATT
CCACGAATAACCATAGAAATGAAAGCAGAGGCAGAAAAGAAAAATAAAAAGAAAATTAAG
AATGAAAATACTGAAGGAAGCCCTCAAGAAGATGGTGTGGAACTAGAAGGCCTAAAACAA
AGATTAGAAAAGAAACAGAAAAGAGAACCAGGTACAAAGACAAAGAAACAAACTACATTG
GCATTTAAGCCAATCAAAAAAGGAAAGAAGAGAAATCCCTGGTCTGATTCAGAATCAGAT
AGGAGCAGTGACGAAAGTAATTTTGATGTCCCTCCACGAGAAACAGAGCCACGGAGAGCA
GCAACAAAAACAAAATTCACAATGGATTTGGATTCAGATGAAGATTTCTCAGATTTTGAT
GAAAAAACTGATGATGAAGATTTTGTCCCATCAGATGCTAGTCCACCTAAGACCAAAACT
TCCCCAAAACTTAGTAACAAAGAACTGAAACCACAGAAAAGTGTCGTGTCAGACCTTGAA
GCTGATGATGTTAAGGGCAGTGTACCACTGTCTTCAAGCCCTCCTGCTACACATTTCCCA
GATGAAACTGAAATTACAAACCCAGTTCCTAAAAAGAATGTGACAGTGAAGAAGACAGCA
GCAAAAAGTCAGTCTTCCACCTCCACTACCGGTGCCAAAAAAAGGGCTGCCCCAAAAGGA
ACTAAAAGGGATCCAGCTTTGAATTCTGGTGTCTCTCAAAAGCCTGATCCTGCCAAAACC
AAGAATCGCCGCAAAAGGAAGCCATCCACTTCTGATGATTCTGACTCTAATTTTGAGAAA
ATTGTTTCGAAAGCAGTCACAAGCAAGAAATCCAAGGGGGAGAGTGATGACTTCCATATG
GACTTTGACTCAGCTGTGGCTCCTCGGGCAAAATCTGTACGGGCAAAGAAACCTATAAAG
TACCTGGAAGAGTCAGATGAAGATGATCTGTTTTAA
GenBank Gene IDJ04088
GeneCard IDNot Available
GenAtlas IDTOP2A
HGNC IDHGNC:11989
Chromosome Location17
Locus17q21-q22
References
  1. Tsai-Pflugfelder M, Liu LF, Liu AA, Tewey KM, Whang-Peng J, Knutsen T, Huebner K, Croce CM, Wang JC: Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7177-81. 2845399
  2. Wasserman RA, Austin CA, Fisher LM, Wang JC: Use of yeast in the study of anticancer drugs targeting DNA topoisomerases: expression of a functional recombinant human DNA topoisomerase II alpha in yeast. Cancer Res. 1993 Aug 1;53(15):3591-6. 8393377
  3. Lang AJ, Mirski SE, Cummings HJ, Yu Q, Gerlach JH, Cole SP: Structural organization of the human TOP2A and TOP2B genes. Gene. 1998 Oct 23;221(2):255-66. 9795238
  4. Sng JH, Heaton VJ, Bell M, Maini P, Austin CA, Fisher LM: Molecular cloning and characterization of the human topoisomerase IIalpha and IIbeta genes: evidence for isoform evolution through gene duplication. Biochim Biophys Acta. 1999 Mar 19;1444(3):395-406. 10095062
  5. Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. 16625196
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  7. Escargueil AE, Plisov SY, Filhol O, Cochet C, Larsen AK: Mitotic phosphorylation of DNA topoisomerase II alpha by protein kinase CK2 creates the MPM-2 phosphoepitope on Ser-1469. J Biol Chem. 2000 Nov 3;275(44):34710-8. 10942766
  8. Mirski SE, Bielawski JC, Cole SP: Identification of functional nuclear export sequences in human topoisomerase IIalpha and beta. Biochem Biophys Res Commun. 2003 Jul 11;306(4):905-11. 12821127
  9. Yun J, Tomida A, Andoh T, Tsuruo T: Interaction between glucose-regulated destruction domain of DNA topoisomerase IIalpha and MPN domain of Jab1/CSN5. J Biol Chem. 2004 Jul 23;279(30):31296-303. Epub 2004 May 4. 15126503
  10. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. 17081983
  11. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10. 16964243
  12. Yu LR, Zhu Z, Chan KC, Issaq HJ, Dimitrov DS, Veenstra TD: Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra. J Proteome Res. 2007 Nov;6(11):4150-62. Epub 2007 Oct 9. 17924679
  13. Iida M, Matsuda M, Komatani H: Plk3 phosphorylates topoisomerase IIalpha at Thr(1342), a site that is not recognized by Plk1. Biochem J. 2008 Apr 1;411(1):27-32. 18062778
  14. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res. 2008 Mar;7(3):1346-51. doi: 10.1021/pr0705441. Epub 2008 Jan 26. 18220336
  15. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. 18691976
  16. Williamson EA, Rasila KK, Corwin LK, Wray J, Beck BD, Severns V, Mobarak C, Lee SH, Nickoloff JA, Hromas R: The SET and transposase domain protein Metnase enhances chromosome decatenation: regulation by automethylation. Nucleic Acids Res. 2008 Oct;36(18):5822-31. doi: 10.1093/nar/gkn560. Epub 2008 Sep 12. 18790802
  17. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  18. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. 19413330
  19. Deweese JE, Burch AM, Burgin AB, Osheroff N: Use of divalent metal ions in the dna cleavage reaction of human type II topoisomerases. Biochemistry. 2009 Mar 10;48(9):1862-9. doi: 10.1021/bi8023256. 19222228
  20. Deweese JE, Guengerich FP, Burgin AB, Osheroff N: Metal ion interactions in the DNA cleavage/ligation active site of human topoisomerase IIalpha. Biochemistry. 2009 Sep 29;48(38):8940-7. doi: 10.1021/bi900875c. 19697956
  21. Grozav AG, Chikamori K, Kozuki T, Grabowski DR, Bukowski RM, Willard B, Kinter M, Andersen AH, Ganapathi R, Ganapathi MK: Casein kinase I delta/epsilon phosphorylates topoisomerase IIalpha at serine-1106 and modulates DNA cleavage activity. Nucleic Acids Res. 2009 Feb;37(2):382-92. doi: 10.1093/nar/gkn934. Epub 2008 Nov 29. 19043076
  22. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  23. De Haro LP, Wray J, Williamson EA, Durant ST, Corwin L, Gentry AC, Osheroff N, Lee SH, Hromas R, Nickoloff JA: Metnase promotes restart and repair of stalled and collapsed replication forks. Nucleic Acids Res. 2010 Sep;38(17):5681-91. doi: 10.1093/nar/gkq339. Epub 2010 May 10. 20457750
  24. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. 20068231
  25. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  26. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. 21406692
  27. Schmidt BH, Osheroff N, Berger JM: Structure of a topoisomerase II-DNA-nucleotide complex reveals a new control mechanism for ATPase activity. Nat Struct Mol Biol. 2012 Nov;19(11):1147-54. doi: 10.1038/nsmb.2388. Epub 2012 Sep 30. 23022727
  28. Ramamoorthy M, Tadokoro T, Rybanska I, Ghosh AK, Wersto R, May A, Kulikowicz T, Sykora P, Croteau DL, Bohr VA: RECQL5 cooperates with Topoisomerase II alpha in DNA decatenation and cell cycle progression. Nucleic Acids Res. 2012 Feb;40(4):1621-35. doi: 10.1093/nar/gkr844. Epub 2011 Oct 19. 22013166
  29. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. 22814378
  30. Lee S, Jung SR, Heo K, Byl JA, Deweese JE, Osheroff N, Hohng S: DNA cleavage and opening reactions of human topoisomerase IIalpha are regulated via Mg2+-mediated dynamic bending of gate-DNA. Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2925-30. doi: 10.1073/pnas.1115704109. Epub 2012 Feb 9. 22323612
  31. Hendriks IA, D'Souza RC, Yang B, Verlaan-de Vries M, Mann M, Vertegaal AC: Uncovering global SUMOylation signaling networks in a site-specific manner. Nat Struct Mol Biol. 2014 Oct;21(10):927-36. doi: 10.1038/nsmb.2890. Epub 2014 Sep 14. 25218447
  32. Wei H, Ruthenburg AJ, Bechis SK, Verdine GL: Nucleotide-dependent domain movement in the ATPase domain of a human type IIA DNA topoisomerase. J Biol Chem. 2005 Nov 4;280(44):37041-7. Epub 2005 Aug 12. 16100112
  33. Wendorff TJ, Schmidt BH, Heslop P, Austin CA, Berger JM: The structure of DNA-bound human topoisomerase II alpha: conformational mechanisms for coordinating inter-subunit interactions with DNA cleavage. J Mol Biol. 2012 Dec 7;424(3-4):109-24. doi: 10.1016/j.jmb.2012.07.014. Epub 2012 Jul 25. 22841979
  34. Hinds M, Deisseroth K, Mayes J, Altschuler E, Jansen R, Ledley FD, Zwelling LA: Identification of a point mutation in the topoisomerase II gene from a human leukemia cell line containing an amsacrine-resistant form of topoisomerase II. Cancer Res. 1991 Sep 1;51(17):4729-31. 1651812
  35. Bugg BY, Danks MK, Beck WT, Suttle DP: Expression of a mutant DNA topoisomerase II in CCRF-CEM human leukemic cells selected for resistance to teniposide. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7654-8. 1652758