DNA binding and RAD51 engagement by the BRCA2 C-terminus orchestrate DNA repair and replication fork preservation.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
26 01 2023
26 01 2023
Historique:
received:
06
09
2022
accepted:
19
01
2023
entrez:
26
1
2023
pubmed:
27
1
2023
medline:
31
1
2023
Statut:
epublish
Résumé
The tumor suppressor BRCA2 participates in DNA double-strand break repair by RAD51-dependent homologous recombination and protects stressed DNA replication forks from nucleolytic attack. We demonstrate that the C-terminal Recombinase Binding (CTRB) region of BRCA2, encoded by gene exon 27, harbors a DNA binding activity. CTRB alone stimulates the DNA strand exchange activity of RAD51 and permits the utilization of RPA-coated ssDNA by RAD51 for strand exchange. Moreover, CTRB functionally synergizes with the Oligonucleotide Binding fold containing DNA binding domain and BRC4 repeat of BRCA2 in RPA-RAD51 exchange on ssDNA. Importantly, we show that the DNA binding and RAD51 interaction attributes of the CTRB are crucial for homologous recombination and protection of replication forks against MRE11-mediated attrition. Our findings shed light on the role of the CTRB region in genome repair, reveal remarkable functional plasticity of BRCA2, and help explain why deletion of Brca2 exon 27 impacts upon embryonic lethality.
Identifiants
pubmed: 36702902
doi: 10.1038/s41467-023-36211-x
pii: 10.1038/s41467-023-36211-x
pmc: PMC9879961
doi:
Substances chimiques
Rad51 Recombinase
EC 2.7.7.-
BRCA2 Protein
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
432Subventions
Organisme : NCI NIH HHS
ID : R01 CA268641
Pays : United States
Organisme : NCI NIH HHS
ID : F30 CA260908
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA148724
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES007061
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA237286
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM141091
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA205224
Pays : United States
Organisme : NIEHS NIH HHS
ID : R56 ES021454
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA246807
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA092584
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA265315
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA168635
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA188347
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM136717
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA241801
Pays : United States
Informations de copyright
© 2023. The Author(s).
Références
Proteins. 2005 Jun 1;59(4):687-96
pubmed: 15815974
Nucleic Acids Res. 2020 Jan 8;48(D1):D835-D844
pubmed: 31777943
Nucleic Acids Res. 2003 Jul 1;31(13):3497-500
pubmed: 12824352
Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10448-53
pubmed: 21670257
J Biol Chem. 2011 Oct 28;286(43):37328-34
pubmed: 21903585
Mol Biol Evol. 2017 Jul 1;34(7):1812-1819
pubmed: 28387841
Genes Dev. 2012 Oct 15;26(20):2337-47
pubmed: 23070815
Genes (Basel). 2021 May 20;12(5):
pubmed: 34065235
Science. 2002 Sep 13;297(5588):1837-48
pubmed: 12228710
Cell. 2011 May 13;145(4):529-42
pubmed: 21565612
Cancer Discov. 2015 Nov;5(11):1137-54
pubmed: 26463832
Mol Cell. 2019 Jun 6;74(5):866-876
pubmed: 31173722
Nat Commun. 2017 Oct 16;8(1):859
pubmed: 29038466
Cancer Res. 2010 Feb 1;70(3):988-95
pubmed: 20103620
Nat Rev Mol Cell Biol. 2006 Oct;7(10):739-50
pubmed: 16926856
Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13254-9
pubmed: 19628690
Nucleic Acids Res. 2016 Jun 20;44(11):5256-70
pubmed: 27084934
Nature. 2017 Oct 19;550(7676):360-365
pubmed: 28976962
Annu Rev Biochem. 2008;77:229-57
pubmed: 18275380
Nature. 2002 Nov 21;420(6913):287-93
pubmed: 12442171
Annu Rev Genet. 2021 Nov 23;55:285-307
pubmed: 34813349
Cancer Res. 1998 Aug 1;58(15):3441-7
pubmed: 9699678
Nucleic Acids Res. 2018 Jul 2;46(W1):W329-W337
pubmed: 29860432
Nature. 2005 Mar 31;434(7033):598-604
pubmed: 15800615
Mol Cell. 2015 Jul 16;59(2):176-87
pubmed: 26145171
EMBO J. 2007 Jun 20;26(12):2915-22
pubmed: 17541404
Clin Cancer Res. 2022 Sep 1;28(17):3742-3751
pubmed: 35736817
Genomics Proteomics Bioinformatics. 2020 Feb;18(1):72-80
pubmed: 32200042
Nature. 2005 Feb 10;433(7026):653-7
pubmed: 15703751
Nat Chem Biol. 2008 Feb;4(2):119-25
pubmed: 18176557
Biomolecules. 2021 Jul 20;11(7):
pubmed: 34356684
Nucleic Acids Res. 2007 Jul;35(Web Server issue):W460-4
pubmed: 17567614
Nature. 2019 Jul;571(7766):521-527
pubmed: 31270457
Cancer Res. 2002 Feb 15;62(4):990-4
pubmed: 11861370
Nat Struct Mol Biol. 2007 Jun;14(6):468-74
pubmed: 17515904
Mol Cell. 2001 Feb;7(2):263-72
pubmed: 11239455
Annu Rev Biochem. 2019 Jun 20;88:221-245
pubmed: 30917004
Nucleic Acids Res. 2015 Nov 16;43(20):9817-34
pubmed: 26323318
Cold Spring Harb Perspect Biol. 2015 Apr 01;7(4):a016600
pubmed: 25833843
Nature. 1997 Apr 24;386(6627):804-10
pubmed: 9126738
Nucleic Acids Res. 2015 Oct 30;43(19):9379-92
pubmed: 26429972
Nature. 2005 Apr 14;434(7035):917-21
pubmed: 15829967
DNA Repair (Amst). 2003 Sep 18;2(9):1015-28
pubmed: 12967658
Nat Commun. 2017 Sep 13;8(1):525
pubmed: 28904335
Nat Commun. 2016 Oct 25;7:13241
pubmed: 27779185
Biochim Biophys Acta. 2010 Apr;1804(4):996-1010
pubmed: 20100603
Prog Nucl Magn Reson Spectrosc. 2011 Oct;59(3):271-92
pubmed: 21920222
Semin Cell Dev Biol. 2021 May;113:14-26
pubmed: 32653304
Mol Microbiol. 2011 Jan;79(1):180-91
pubmed: 21166902
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W325-30
pubmed: 24880689
PLoS Genet. 2011 Dec;7(12):e1002409
pubmed: 22194698
Genes Chromosomes Cancer. 2003 Apr;36(4):317-31
pubmed: 12619154
Nucleic Acids Res. 2019 Jan 8;47(D1):D506-D515
pubmed: 30395287
J Biomol NMR. 1995 Nov;6(3):277-93
pubmed: 8520220
Biophys Chem. 2017 Jun;225:27-37
pubmed: 27974172
Protein Sci. 2006 Dec;15(12):2795-804
pubmed: 17088319
J Biol Chem. 2006 Apr 28;281(17):11649-57
pubmed: 16513631
Genomics Proteomics Bioinformatics. 2019 Dec;17(6):645-656
pubmed: 32173600
Elife. 2021 Jul 13;10:
pubmed: 34254584
J Biomol NMR. 1991 May;1(1):99-104
pubmed: 1668719
Methods Mol Biol. 2011;745:421-35
pubmed: 21660708
Methods Enzymol. 2018;600:179-199
pubmed: 29458758
J Biomol NMR. 1995 Sep;6(2):135-40
pubmed: 8589602
Nat Rev Mol Cell Biol. 2020 May;21(5):284-299
pubmed: 32094664
Nature. 2010 Oct 7;467(7316):678-83
pubmed: 20729832
Intrinsically Disord Proteins. 2013 Apr 1;1(1):e24428
pubmed: 28516009
Cell. 2009 Mar 20;136(6):1032-43
pubmed: 19303847
J Biol Chem. 2001 Mar 23;276(12):8798-806
pubmed: 11124265
Nat Struct Mol Biol. 2007 Jun;14(6):475-83
pubmed: 17515903
Mutat Res. 2014 Aug-Sep;766-767:66-72
pubmed: 25773776
Sci Rep. 2017 Jan 31;7:41553
pubmed: 28139687
Mol Cell. 2017 Oct 19;68(2):414-430.e8
pubmed: 29053959
DNA Repair (Amst). 2015 Aug;32:66-74
pubmed: 25956866
Bioinformatics. 2007 Aug 1;23(15):1875-82
pubmed: 17519246
Nat Rev Mol Cell Biol. 2019 Nov;20(11):698-714
pubmed: 31263220