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dc.contributor.authorVincendeau, Estelle
dc.contributor.authorWei, Wenming
dc.contributor.authorZhang, Xuefei
dc.contributor.authorPlanchais, Cyril
dc.contributor.authorYu, Wei
dc.contributor.authorLenden-Hasse, Hélène
dc.contributor.authorCokelaer, Thomas
dc.contributor.authorPipoli da Fonseca, Juliana
dc.contributor.authorMouquet, Hugo
dc.contributor.authorAdams, David J
dc.contributor.authorAlt, Frederick W
dc.contributor.authorJackson, Stephen
dc.contributor.authorBalmus, Gabriel
dc.contributor.authorLescale, Chloé
dc.contributor.authorDeriano, Ludovic
dc.date.accessioned2022-06-29T19:49:58Z
dc.date.available2022-06-29T19:49:58Z
dc.date.issued2022-06-28
dc.date.submitted2021-07-27
dc.identifier.issn2041-1723
dc.identifier.others41467-022-31287-3
dc.identifier.other31287
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338596
dc.descriptionFunder: Ligue Nationale Contre le Cancer
dc.description.abstractSHLD1 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.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/250/2152/2498
dc.subject/631/337/1427/2122
dc.subject/631/337/149
dc.subject/631/250/2152/2497
dc.subject/13/1
dc.subject/13/21
dc.subject/13/31
dc.subject/13/106
dc.subject/45
dc.subject/45/23
dc.subject/45/71
dc.subject/45/77
dc.subject/49
dc.subjectarticle
dc.titleSHLD1 is dispensable for 53BP1-dependent V(D)J recombination but critical for productive class switch recombination.
dc.typeArticle
dc.date.updated2022-06-29T19:49:56Z
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume13
dc.identifier.doi10.17863/CAM.86009
dcterms.dateAccepted2022-06-13
rioxxterms.versionofrecord10.1038/s41467-022-31287-3
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidVincendeau, Estelle [0000-0002-0231-1609]
dc.contributor.orcidZhang, Xuefei [0000-0002-1873-6679]
dc.contributor.orcidYu, Wei [0000-0002-1777-5254]
dc.contributor.orcidCokelaer, Thomas [0000-0001-6286-1138]
dc.contributor.orcidAdams, David J [0000-0001-9490-0306]
dc.contributor.orcidJackson, Stephen [0000-0001-9317-7937]
dc.contributor.orcidBalmus, Gabriel [0000-0003-2872-4468]
dc.contributor.orcidLescale, Chloé [0000-0003-0622-1149]
dc.contributor.orcidDeriano, Ludovic [0000-0002-9673-9525]
dc.identifier.eissn2041-1723
pubs.funder-project-idCancer Research UK (C6946/A24843)
pubs.funder-project-idWellcome Trust (203144/Z/16/Z)
pubs.funder-project-idWellcome Trust (206388/Z/17/Z)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) ERC (855741)
cam.issuedOnline2022-06-28


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