SHLD1 is dispensable for 53BP1-dependent V(D)J recombination but critical for productive class switch recombination.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 06 2022
28 06 2022
Historique:
received:
27
07
2021
accepted:
13
06
2022
entrez:
28
6
2022
pubmed:
29
6
2022
medline:
1
7
2022
Statut:
epublish
Résumé
SHLD1 is part of the Shieldin (SHLD) complex, which acts downstream of 53BP1 to counteract DNA double-strand break (DSB) end resection and promote DNA repair via non-homologous end-joining (NHEJ). While 53BP1 is essential for immunoglobulin heavy chain class switch recombination (CSR), long-range V(D)J recombination and repair of RAG-induced DSBs in XLF-deficient cells, the function of SHLD during these processes remains elusive. Here we report that SHLD1 is dispensable for lymphocyte development and RAG-mediated V(D)J recombination, even in the absence of XLF. By contrast, SHLD1 is essential for restricting resection at AID-induced DSB ends in both NHEJ-proficient and NHEJ-deficient B cells, providing an end-protection mechanism that permits productive CSR by NHEJ and alternative end-joining. Finally, we show that this SHLD1 function is required for orientation-specific joining of AID-initiated DSBs. Our data thus suggest that 53BP1 promotes V(D)J recombination and CSR through two distinct mechanisms: SHLD-independent synapsis of V(D)J segments and switch regions within chromatin, and SHLD-dependent protection of AID-DSB ends against resection.
Identifiants
pubmed: 35764636
doi: 10.1038/s41467-022-31287-3
pii: 10.1038/s41467-022-31287-3
pmc: PMC9240092
doi:
Substances chimiques
DNA-Binding Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3707Subventions
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : Cancer Research UK
ID : DRCPGM\100005
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C6946/A24843
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206388/Z/17/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203144
Pays : United Kingdom
Organisme : Howard Hughes Medical Institute
Pays : United States
Informations de copyright
© 2022. The Author(s).
Références
EMBO J. 2018 Sep 14;37(18):
pubmed: 30154076
Nature. 2011 Jun 15;474(7351):337-42
pubmed: 21677750
Nature. 2007 Sep 27;449(7161):478-82
pubmed: 17713479
Nat Commun. 2020 Oct 16;11(1):5239
pubmed: 33067475
Nat Struct Mol Biol. 2016 Aug;23(8):714-21
pubmed: 27348077
Nature. 2015 May 28;521(7553):541-544
pubmed: 25799992
J Immunol. 2014 Dec 1;193(11):5370-8
pubmed: 25411432
Nat Immunol. 2004 May;5(5):481-7
pubmed: 15077110
Mol Cell. 2021 Jun 17;81(12):2611-2624.e10
pubmed: 33857404
Nature. 2015 Sep 3;525(7567):134-139
pubmed: 26308889
Nat Commun. 2016 Feb 02;7:10529
pubmed: 26833222
DNA Repair (Amst). 2020 Oct;94:102874
pubmed: 32623318
Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3903-8
pubmed: 22355127
Mol Cell Biol. 2013 Feb;33(4):701-11
pubmed: 23207905
Cell Rep. 2016 Sep 13;16(11):2967-2979
pubmed: 27601299
Mol Cell Biol. 2003 Apr;23(7):2556-63
pubmed: 12640136
Cell. 2013 Jul 18;154(2):452-64
pubmed: 23870131
Nucleic Acids Res. 2015 Jan;43(Database issue):D512-20
pubmed: 25514926
Annu Rev Genet. 2011;45:167-202
pubmed: 21854230
Cell. 2018 Jan 25;172(3):465-477.e15
pubmed: 29358048
Front Genet. 2022 Jan 05;12:823943
pubmed: 35082840
Proc Natl Acad Sci U S A. 2006 May 9;103(19):7378-83
pubmed: 16670198
Proc Natl Acad Sci U S A. 2016 Sep 20;113(38):10619-24
pubmed: 27601633
Proc Natl Acad Sci U S A. 2020 Oct 13;117(41):25700-25711
pubmed: 32989150
Proc Natl Acad Sci U S A. 2018 Jan 23;115(4):762-767
pubmed: 29311308
Cell Rep. 2013 Jan 31;3(1):138-47
pubmed: 23291097
Science. 2013 Feb 8;339(6120):711-5
pubmed: 23306439
J Exp Med. 2010 Feb 15;207(2):417-27
pubmed: 20142431
J Cell Biol. 2004 May 24;165(4):459-64
pubmed: 15159415
Nature. 2018 Aug;560(7716):122-127
pubmed: 30046110
Cell. 2004 Jun 11;117(6):787-800
pubmed: 15186779
EMBO Rep. 2020 Aug 5;21(8):e49823
pubmed: 32558186
Cell. 2018 May 3;173(4):972-988.e23
pubmed: 29656893
Proc Natl Acad Sci U S A. 2021 Jan 19;118(3):
pubmed: 33441485
J Immunol Methods. 2017 Dec;451:71-77
pubmed: 28882611
Nature. 2019 Nov;575(7782):385-389
pubmed: 31666703
Nat Commun. 2022 Feb 21;13(1):980
pubmed: 35190531
Nat Rev Immunol. 2022 Feb 15;:
pubmed: 35169260
Mol Cell. 2022 Apr 7;82(7):1359-1371.e9
pubmed: 35216668
Cell. 1996 Jul 12;86(1):159-71
pubmed: 8689683
Nat Commun. 2021 Sep 14;12(1):5421
pubmed: 34521823
Trends Immunol. 2020 Jul;41(7):586-600
pubmed: 32434680
Cell Res. 2020 Sep;30(9):732-744
pubmed: 32355287
Mech Ageing Dev. 2017 Jul;165(Pt A):3-9
pubmed: 27863852
Cell. 2010 Apr 2;141(1):27-38
pubmed: 20371343
Nature. 2006 Jul 27;442(7101):466-70
pubmed: 16799570
Nat Cell Biol. 2022 Jan;24(1):51-61
pubmed: 35027730
Cell. 2013 Jan 31;152(3):417-29
pubmed: 23374339
Nature. 2015 May 28;521(7553):537-540
pubmed: 25799990
Mol Cell. 2018 Jul 19;71(2):332-342.e8
pubmed: 30017584
Proc Natl Acad Sci U S A. 2021 May 25;118(21):
pubmed: 34006647
Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2455-60
pubmed: 22308489
Nat Cell Biol. 2020 Jan;22(1):87-96
pubmed: 31915374
Trends Cell Biol. 2021 Dec;31(12):965-978
pubmed: 34147298
Nat Cell Biol. 2018 Aug;20(8):954-965
pubmed: 30022119
Nat Commun. 2017 Feb 08;8:14244
pubmed: 28176781
Mol Cell. 2013 Mar 7;49(5):858-71
pubmed: 23333305
Nature. 2008 Nov 27;456(7221):529-33
pubmed: 18931658
Annu Rev Immunol. 2012;30:175-202
pubmed: 22224778
Nat Commun. 2017 Jan 04;8:13816
pubmed: 28051062
Nature. 2018 Aug;560(7716):117-121
pubmed: 30022168
Eur J Immunol. 2007 Jan;37(1):235-9
pubmed: 17183606
Nature. 2011 Jan 13;469(7329):250-4
pubmed: 21160472
EMBO Rep. 2019 May;20(5):
pubmed: 30948458
Bioinformatics. 2018 Sep 15;34(18):3094-3100
pubmed: 29750242
Mamm Genome. 2012 Oct;23(9-10):580-6
pubmed: 22968824
Adv Immunol. 2012;116:1-49
pubmed: 23063072
Cell Rep. 2019 Aug 6;28(6):1389-1399.e6
pubmed: 31390554
Nat Commun. 2018 Sep 25;9(1):3925
pubmed: 30254264
Nat Protoc. 2016 May;11(5):853-71
pubmed: 27031497
Trends Biochem Sci. 2021 Mar;46(3):184-199
pubmed: 33250286
Genes Dev. 2020 Jan 1;34(1-2):7-23
pubmed: 31896689
Nature. 2019 Oct;574(7779):571-574
pubmed: 31645724
Annu Rev Genet. 2013;47:433-55
pubmed: 24050180
Cell. 2002 Apr;109 Suppl:S45-55
pubmed: 11983152
DNA Repair (Amst). 2014 Apr;16:11-22
pubmed: 24674624