Polymerase theta-helicase promotes end joining by stripping single-stranded DNA-binding proteins and bridging DNA ends.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
22 04 2022
22 04 2022
Historique:
accepted:
29
03
2022
revised:
20
01
2022
received:
03
06
2021
pubmed:
1
4
2022
medline:
26
4
2022
entrez:
31
3
2022
Statut:
ppublish
Résumé
Homologous recombination-deficient cancers rely on DNA polymerase Theta (Polθ)-Mediated End Joining (TMEJ), an alternative double-strand break repair pathway. Polθ is the only vertebrate polymerase that encodes an N-terminal superfamily 2 (SF2) helicase domain, but the role of this helicase domain in TMEJ remains unclear. Using single-molecule imaging, we demonstrate that Polθ-helicase (Polθ-h) is a highly processive single-stranded DNA (ssDNA) motor protein that can efficiently strip Replication Protein A (RPA) from ssDNA. Polθ-h also has a limited capacity for disassembling RAD51 filaments but is not processive on double-stranded DNA. Polθ-h can bridge two non-complementary DNA strands in trans. PARylation of Polθ-h by PARP-1 resolves these DNA bridges. We conclude that Polθ-h removes RPA and RAD51 filaments and mediates bridging of DNA overhangs to aid in polymerization by the Polθ polymerase domain.
Identifiants
pubmed: 35357490
pii: 6561656
doi: 10.1093/nar/gkac119
pmc: PMC9023281
doi:
Substances chimiques
DNA, Single-Stranded
0
DNA-Binding Proteins
0
Replication Protein A
0
DNA
9007-49-2
DNA Helicases
EC 3.6.4.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
3911-3921Subventions
Organisme : NCI NIH HHS
ID : P01 CA092584
Pays : United States
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.
Références
Essays Biochem. 2020 Oct 26;64(5):779-790
pubmed: 32756864
DNA Repair (Amst). 2015 Aug;32:10-16
pubmed: 25963443
Trends Genet. 2019 Sep;35(9):632-644
pubmed: 31296341
Methods Mol Biol. 2011;780:209-26
pubmed: 21870263
EMBO J. 2017 Dec 15;36(24):3634-3649
pubmed: 29079701
Nucleic Acids Res. 2020 Aug 20;48(14):7834-7843
pubmed: 32621611
PLoS One. 2014 Feb 03;9(2):e87922
pubmed: 24498402
DNA Repair (Amst). 2016 Aug;44:22-32
pubmed: 27264557
Annu Rev Biochem. 2021 Jun 20;90:137-164
pubmed: 33556282
Proc Natl Acad Sci U S A. 2020 Apr 14;117(15):8476-8485
pubmed: 32234782
Nat Commun. 2014;5:3216
pubmed: 24496117
Langmuir. 2018 Dec 11;34(49):14882-14890
pubmed: 30044093
Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13390-5
pubmed: 20624954
J Mol Biol. 2014 Jun 26;426(13):2413-21
pubmed: 24792418
Genome Res. 2014 Jun;24(6):954-62
pubmed: 24614976
Annu Rev Genet. 2011;45:247-71
pubmed: 21910633
Mol Cell Proteomics. 2019 May;18(5):1010-1026
pubmed: 30798302
J Biol Chem. 2018 Jul 6;293(27):10536-10546
pubmed: 29530982
Cancer Res. 2010 Apr 1;70(7):2984-93
pubmed: 20233878
Methods Enzymol. 2017;592:103-121
pubmed: 28668117
Proc Natl Acad Sci U S A. 2015 Dec 15;112(50):E6852-61
pubmed: 26540728
Nat Struct Mol Biol. 2017 Dec;24(12):1116-1123
pubmed: 29058711
FEMS Microbiol Rev. 2014 Mar;38(2):172-84
pubmed: 24483249
Trends Biochem Sci. 2015 Nov;40(11):701-714
pubmed: 26439531
Trends Cancer. 2021 Feb;7(2):98-111
pubmed: 33109489
Oncotarget. 2010 Jul;1(3):175-84
pubmed: 20700469
Soft Matter. 2011 Jan 1;7(18):8005-8012
pubmed: 22956981
J Biol Chem. 1997 Mar 21;272(12):7940-5
pubmed: 9065463
J Mol Recognit. 2009 Nov-Dec;22(6):446-52
pubmed: 19585541
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Mol Cell. 2010 Nov 24;40(4):521-32
pubmed: 21095583
Nucleic Acids Res. 2003 Nov 1;31(21):6117-26
pubmed: 14576298
Mol Cell. 2019 Jul 11;75(1):145-153.e5
pubmed: 31153714
Curr Biol. 2001 Nov 13;11(22):R920-4
pubmed: 11719239
J Mol Biol. 2014 Sep 23;426(19):3246-3261
pubmed: 25058683
Annu Rev Genet. 2016 Nov 23;50:393-421
pubmed: 27893960
Proc Natl Acad Sci U S A. 2013 May 7;110(19):7720-5
pubmed: 23610439
Biochim Biophys Acta. 1999 Feb 10;1430(1):119-26
pubmed: 10082940
Nat Cancer. 2021 Jun;2(6):598-610
pubmed: 34179826
Nature. 2015 Feb 12;518(7538):258-62
pubmed: 25642963
J Biol Chem. 2018 Apr 6;293(14):5259-5269
pubmed: 29444826
Genes (Basel). 2016 Sep 21;7(9):
pubmed: 27657134
Methods Enzymol. 2017;592:259-281
pubmed: 28668123
Nat Struct Mol Biol. 2015 Mar;22(3):230-7
pubmed: 25643323
Nat Struct Mol Biol. 2007 Jul;14(7):647-52
pubmed: 17558417
Mol Cell Biol. 2013 Nov;33(22):4492-503
pubmed: 24043304
Mol Cell. 2017 Jan 19;65(2):260-271
pubmed: 28107648
Nat Struct Mol Biol. 2019 Feb;26(2):129-136
pubmed: 30723327
Nucleic Acids Res. 2017 Mar 17;45(5):2585-2599
pubmed: 27994036
Methods Enzymol. 2019;616:43-59
pubmed: 30691654
Structure. 2015 Dec 1;23(12):2319-2330
pubmed: 26636256
Transl Cancer Res. 2013 Jun;2(3):130-143
pubmed: 24000320
Nat Struct Mol Biol. 2014 Apr;21(4):405-12
pubmed: 24608368
Cell. 2010 Sep 17;142(6):943-53
pubmed: 20832105
DNA Repair (Amst). 2006 Mar 7;5(3):381-91
pubmed: 16388992
EMBO J. 2018 Apr 3;37(7):
pubmed: 29507080
Nucleic Acids Res. 2006;34(21):6170-82
pubmed: 17088286
Nature. 2015 Feb 12;518(7538):254-7
pubmed: 25642960
Int J Cancer. 2004 Mar;109(1):9-16
pubmed: 14735462
Nat Commun. 2019 Jul 4;10(1):2954
pubmed: 31273204
Mol Cell. 2016 Mar 17;61(6):850-8
pubmed: 26990988
DNA Repair (Amst). 2013 Jan 1;12(1):1-9
pubmed: 23219161
Nature. 2010 Oct 7;467(7316):678-83
pubmed: 20729832
Langmuir. 2015 Sep 22;31(37):10310-7
pubmed: 26325477
Nat Commun. 2019 Sep 19;10(1):4286
pubmed: 31537809
Mol Cell. 2016 Aug 18;63(4):662-673
pubmed: 27453047
Proc Natl Acad Sci U S A. 2018 Jul 24;115(30):7747-7752
pubmed: 29987024
Nucleic Acids Res. 2017 Jan 25;45(2):749-761
pubmed: 27903895
Nucleic Acids Res. 2018 Apr 20;46(7):3446-3457
pubmed: 29447383