Naturally mutagenic sequence diversity in a human type II topoisomerase.
DNA damage
cancer
chemotherapeutic
protein dynamics
topoisomerase
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:
11 07 2023
11 07 2023
Historique:
pmc-release:
05
01
2024
medline:
7
7
2023
pubmed:
5
7
2023
entrez:
5
7
2023
Statut:
ppublish
Résumé
Type II topoisomerases transiently cleave duplex DNA as part of a strand passage mechanism that helps control chromosomal organization and superstructure. Aberrant DNA cleavage can result in genomic instability, and how topoisomerase activity is controlled to prevent unwanted breaks is poorly understood. Using a genetic screen, we identified mutations in the beta isoform of human topoisomerase II (hTOP2β) that render the enzyme hypersensitive to the chemotherapeutic agent etoposide. Several of these variants were unexpectedly found to display hypercleavage behavior in vitro and to be capable of inducing cell lethality in a DNA repair-deficient background; surprisingly, a subset of these mutations were also observed in
Identifiants
pubmed: 37406101
doi: 10.1073/pnas.2302064120
pmc: PMC10334734
doi:
Substances chimiques
Mutagens
0
Topoisomerase II Inhibitors
0
Etoposide
6PLQ3CP4P3
DNA Topoisomerases, Type II
EC 5.99.1.3
DNA
9007-49-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2302064120Subventions
Organisme : NCI NIH HHS
ID : R01 CA077373
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008403
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM135131
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA263778
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM116961
Pays : United States
Organisme : NCI NIH HHS
ID : R03 CA216010
Pays : United States
Références
Chem Biol. 2010 May 28;17(5):421-33
pubmed: 20534341
Mol Pharmacol. 1998 Jul;54(1):78-85
pubmed: 9658192
Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):7821-6
pubmed: 12060727
Nat Rev Cancer. 2009 May;9(5):338-50
pubmed: 19377506
DNA Repair (Amst). 2020 Oct;94:102900
pubmed: 32653827
Science. 1979 Nov 30;206(4422):1081-3
pubmed: 227059
Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11014-9
pubmed: 17578914
Curr Biol. 2009 Aug 25;19(16):R676-7
pubmed: 19706272
Cell. 2013 Apr 11;153(2):293-305
pubmed: 23582321
Cancer Chemother Pharmacol. 1994;34(3):242-8
pubmed: 8004758
Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6620-5
pubmed: 19351898
Clin Cancer Res. 2011 Jun 15;17(12):3858-64
pubmed: 21385925
Proc Natl Acad Sci U S A. 2022 Jan 25;119(4):
pubmed: 35058360
Annu Rev Biochem. 2013;82:139-70
pubmed: 23495937
Genes Chromosomes Cancer. 2014 Feb;53(2):117-28
pubmed: 24327541
Nat Struct Mol Biol. 2012 Nov;19(11):1147-54
pubmed: 23022727
Nucleic Acids Res. 2009 Feb;37(3):738-48
pubmed: 19042970
BMC Bioinformatics. 2008 Jan 23;9:40
pubmed: 18215316
Nucleic Acids Res. 1990 Oct 25;18(20):6069-74
pubmed: 2235490
J Comput Chem. 2005 Dec;26(16):1781-802
pubmed: 16222654
Proc Natl Acad Sci U S A. 2019 Sep 17;116(38):18962-18970
pubmed: 31462496
Cancer Res. 1991 Sep 1;51(17):4729-31
pubmed: 1651812
Br J Cancer. 2004 Jul 19;91(2):355-8
pubmed: 15188009
Gene. 1992 Jan 2;110(1):119-22
pubmed: 1544568
Mol Gen Genet. 1996 Aug 27;252(1-2):79-86
pubmed: 8804406
J Biol Chem. 1995 Sep 1;270(35):20359-64
pubmed: 7657608
J Biol Chem. 2008 Oct 24;283(43):29239-50
pubmed: 18723844
Oncol Res. 1995;7(2):103-11
pubmed: 7579726
Science. 1991 Dec 13;254(5038):1598-603
pubmed: 1749933
Cancer Discov. 2012 May;2(5):401-4
pubmed: 22588877
Nucleic Acids Res. 2006 Mar 20;34(5):1597-607
pubmed: 16549872
J Biol Chem. 2008 Aug 29;283(35):23711-20
pubmed: 18596031
Appl Microbiol Biotechnol. 2011 Nov;92(3):479-97
pubmed: 21904817
Annu Rev Pharmacol Toxicol. 2001;41:53-77
pubmed: 11264450
DNA Repair (Amst). 2019 Oct;82:102639
pubmed: 31437813
J Mol Biol. 2019 Aug 23;431(18):3427-3449
pubmed: 31301408
Ann N Y Acad Sci. 2014 Mar;1310:98-110
pubmed: 24495080
Proc Natl Acad Sci U S A. 2020 Oct 27;117(43):26876-26884
pubmed: 33046655
J Biol Chem. 1995 Jan 27;270(4):1913-20
pubmed: 7829529
Nucleic Acids Res. 2019 Sep 5;47(15):8163-8179
pubmed: 31287876
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
Cancer Chemother Pharmacol. 1997;39(4):367-75
pubmed: 9025779
Nat Rev Mol Cell Biol. 2016 Nov;17(11):703-721
pubmed: 27649880
Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7654-8
pubmed: 1652758
Cell. 1994 May 20;77(4):609-16
pubmed: 8187179
Int J Environ Res Public Health. 2012 Jun;9(6):2075-91
pubmed: 22829791
Proc Natl Acad Sci U S A. 1984 Mar;81(5):1361-5
pubmed: 6324188
Cell. 1988 Nov 4;55(3):413-25
pubmed: 2902925