Topoisomerase IIα is essential for maintenance of mitotic chromosome structure.
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
02 06 2020
02 06 2020
Historique:
pubmed:
18
5
2020
medline:
19
8
2020
entrez:
17
5
2020
Statut:
ppublish
Résumé
Topoisomerase IIα (TOP2A) is a core component of mitotic chromosomes and important for establishing mitotic chromosome condensation. The primary roles of TOP2A in mitosis have been difficult to decipher due to its multiple functions across the cell cycle. To more precisely understand the role of TOP2A in mitosis, we used the auxin-inducible degron (AID) system to rapidly degrade the protein at different stages of the human cell cycle. Removal of TOP2A prior to mitosis does not affect prophase timing or the initiation of chromosome condensation. Instead, it prevents chromatin condensation in prometaphase, extends the length of prometaphase, and ultimately causes cells to exit mitosis without chromosome segregation occurring. Surprisingly, we find that removal of TOP2A from cells arrested in prometaphase or metaphase cause dramatic loss of compacted mitotic chromosome structure and conclude that TOP2A is crucial for maintenance of mitotic chromosomes. Treatments with drugs used to poison/inhibit TOP2A function, such as etoposide and ICRF-193, do not phenocopy the effects on chromosome structure of TOP2A degradation by AID. Our data point to a role for TOP2A as a structural chromosome maintenance enzyme locking in condensation states once sufficient compaction is achieved.
Identifiants
pubmed: 32414923
pii: 2001760117
doi: 10.1073/pnas.2001760117
pmc: PMC7275761
doi:
Substances chimiques
Heterochromatin
0
DNA Topoisomerases, Type II
EC 5.99.1.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12131-12142Déclaration de conflit d'intérêts
The authors declare no competing interest.
Références
Cell Growth Differ. 1996 Jan;7(1):83-90
pubmed: 8788036
Nature. 2014 Oct 30;514(7524):646-9
pubmed: 25156254
Nucleic Acids Res. 2014 Apr;42(7):4414-26
pubmed: 24476913
Cell. 1997 Aug 22;90(4):625-34
pubmed: 9288743
Cell Rep. 2016 Apr 5;15(1):210-218
pubmed: 27052166
Trends Cell Biol. 2002 Jun;12(6):281-7
pubmed: 12074888
Mol Biol Cell. 2006 May;17(5):2287-302
pubmed: 16510521
Cell Cycle. 2011 Oct 15;10(20):3505-14
pubmed: 22067657
Cell. 2010 Sep 3;142(5):810-21
pubmed: 20813266
Prog Nucleic Acid Res Mol Biol. 2000;64:221-53
pubmed: 10697411
Chem Biol. 2010 May 28;17(5):421-33
pubmed: 20534341
Cell. 2007 Jan 12;128(1):101-14
pubmed: 17218258
J Cell Biol. 1997 Feb 24;136(4):775-88
pubmed: 9049244
Science. 2018 Feb 9;359(6376):
pubmed: 29348367
J Cell Sci. 2010 Mar 1;123(Pt 5):806-13
pubmed: 20144989
J Cell Biol. 1986 Dec;103(6 Pt 2):2569-81
pubmed: 3025219
Cell Cycle. 2016 Oct 17;15(20):2704-11
pubmed: 27565185
Curr Biol. 2001 May 1;11(9):671-83
pubmed: 11369230
Dev Cell. 2003 Aug;5(2):323-36
pubmed: 12919682
PLoS Genet. 2013 Apr;9(4):e1003463
pubmed: 23637630
Mol Cell. 2004 Sep 24;15(6):977-90
pubmed: 15383286
Oncogene. 2015 Jul 30;34(31):4019-31
pubmed: 25328138
EMBO J. 2007 Jul 25;26(14):3397-409
pubmed: 17599064
Nature. 1994 Dec 1;372(6505):467-70
pubmed: 7984241
Cell. 2015 May 21;161(5):1124-1137
pubmed: 26000485
J Cell Biol. 2010 Mar 8;188(5):653-63
pubmed: 20194637
PLoS Biol. 2008 Aug 26;6(8):e207
pubmed: 18752348
Dev Cell. 2003 Apr;4(4):467-80
pubmed: 12689587
J Biol Chem. 1998 Dec 11;273(50):33660-6
pubmed: 9837951
Nat Rev Cancer. 2009 May;9(5):327-37
pubmed: 19377505
Nanoscale. 2017 Feb 2;9(5):1862-1870
pubmed: 28094382
J Biol Chem. 2001 Nov 30;276(48):44488-94
pubmed: 11577077
J Cell Sci. 2004 Dec 15;117(Pt 26):6435-45
pubmed: 15572404
J Cell Biol. 2003 Jul 21;162(2):245-56
pubmed: 12876275
Annu Rev Genomics Hum Genet. 2006;7:301-13
pubmed: 16756479
Nucleic Acids Res. 2009 Aug;37(14):e98
pubmed: 19494182
Nucleic Acids Res. 2014 Jan;42(1):340-8
pubmed: 24062159
PLoS Genet. 2008 Oct;4(10):e1000228
pubmed: 18927632
Cell Rep. 2015 Dec 22;13(11):2336-2344
pubmed: 26686624
Cell. 1991 Jan 11;64(1):137-48
pubmed: 1846085
Chromosome Res. 2016 May;24(2):243-69
pubmed: 27008552
Elife. 2017 May 06;6:
pubmed: 28477406
Nat Struct Biol. 2001 Jul;8(7):606-10
pubmed: 11427891
Nat Cell Biol. 2006 Oct;8(10):1133-42
pubmed: 16998479
Science. 2011 Mar 11;331(6022):1328-32
pubmed: 21393545
J Cell Biol. 1985 May;100(5):1716-25
pubmed: 2985626
J Cell Biol. 1985 May;100(5):1706-15
pubmed: 2985625
Oncogene. 2010 Aug 26;29(34):4787-99
pubmed: 20562910
J Biol Chem. 2002 Sep 27;277(39):36832-8
pubmed: 12147700
J Cell Biol. 2018 Jul 2;217(7):2309-2328
pubmed: 29632028
J Cell Biol. 1997 Oct 6;139(1):1-12
pubmed: 9314524
J Cell Biol. 1993 Feb;120(3):601-12
pubmed: 8381118
J Cell Sci. 2018 Mar 22;131(6):
pubmed: 29487178
Nat Cell Biol. 2016 Jun;18(6):692-9
pubmed: 27136266
Nature. 2016 Jun 29;535(7611):308-12
pubmed: 27362226
Nat Methods. 2009 Dec;6(12):917-22
pubmed: 19915560
J Cell Sci. 2012 Mar 15;125(Pt 6):1591-604
pubmed: 22344259
J Cell Biol. 2002 Apr 1;157(1):31-44
pubmed: 11927602
J Cell Sci. 2007 Nov 15;120(Pt 22):3952-64
pubmed: 17956945
Nat Cell Biol. 2015 Aug;17(8):1014-23
pubmed: 26075356
J Cell Biol. 2002 Jul 8;158(1):23-9
pubmed: 12105179
J Cell Biol. 2012 Nov 26;199(5):755-70
pubmed: 23166350
Nat Protoc. 2013 Nov;8(11):2281-2308
pubmed: 24157548
Elife. 2014 May 27;3:e01641
pubmed: 24867636
J Cell Biol. 1996 Sep;134(5):1097-107
pubmed: 8794854
Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12044-9
pubmed: 11593014
Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1781-5
pubmed: 8127881
Cell. 1977 Nov;12(3):817-28
pubmed: 922894
Mol Cell. 2016 Oct 6;64(1):134-147
pubmed: 27716481
Cell. 2003 Oct 3;115(1):109-21
pubmed: 14532007
J Cell Biol. 1990 Nov;111(5 Pt 1):1753-62
pubmed: 2172257
Cell. 1994 May 20;77(4):609-16
pubmed: 8187179
Curr Biol. 2011 Jun 21;21(12):1018-24
pubmed: 21658943
Nucleic Acids Res. 2007;35(11):3810-22
pubmed: 17526531