A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs

Garcia-Muse et al. show that the checkpoint kinases ATM and ATR respond to excessive or unrepaired meiotic DSBs by phosphorylating the core synaptonemal complex, which channels repair via the sister chromatid. These findings reveal a mechanism that switches repair partner bias to protect meiotic cel...

Descripción completa

Detalles Bibliográficos
Autores: García-Muse, Tatiana, Galindo-Díaz, Ulises, García-Rubio, María L., Martin, Julie S., Polanowska, Jolanta, O'Reilly, Nicola J., Aguilera, Andrés, Boulton, Simon J.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/202497
Acceso en línea:http://hdl.handle.net/10261/202497
Access Level:acceso abierto
Palabra clave:Meiosis
DNA damage response
ATR/ATM
DNA double-strand breaks
Synaptonemal complex
Inter-sister repair
BRC-1
id ES_d765e90ed4e7f9ad0b514de4d84cfb4a
oai_identifier_str oai:digital.csic.es:10261/202497
network_acronym_str ES
network_name_str España
repository_id_str
spelling A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBsGarcía-Muse, TatianaGalindo-Díaz, UlisesGarcía-Rubio, María L.Martin, Julie S.Polanowska, JolantaO'Reilly, Nicola J.Aguilera, AndrésBoulton, Simon J.MeiosisDNA damage responseATR/ATMDNA double-strand breaksSynaptonemal complexInter-sister repairBRC-1Garcia-Muse et al. show that the checkpoint kinases ATM and ATR respond to excessive or unrepaired meiotic DSBs by phosphorylating the core synaptonemal complex, which channels repair via the sister chromatid. These findings reveal a mechanism that switches repair partner bias to protect meiotic cells from unscheduled DNA breaks.Accurate meiotic chromosome segregation critically depends on the formation of inter-homolog crossovers initiated by double-strand breaks (DSBs). Inaccuracies in this process can drive aneuploidy and developmental defects, but how meiotic cells are protected from unscheduled DNA breaks remains unexplored. Here we define a checkpoint response to persistent meiotic DSBs in C. elegans that phosphorylates the synaptonemal complex (SC) to switch repair partner from the homolog to the sister chromatid. A key target of this response is the core SC component SYP-1, which is phosphorylated in response to ionizing radiation (IR) or unrepaired meiotic DSBs. Failure to phosphorylate (syp-1) or dephosphorylate (syp-1) SYP-1 in response to DNA damage results in chromosome non-dysjunction, hyper-sensitivity to IR-induced DSBs, and synthetic lethality with loss of brc-1. Since BRC-1 is required for inter-sister repair, these observations reveal that checkpoint-dependent SYP-1 phosphorylation safeguards the germline against persistent meiotic DSBs by channelling repair to the sister chromatid.Boulton lab work is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC0010048), the UK Medical Research Council (FC0010048), and the Wellcome Trust (FC0010048). S.J.B. is also the recipient of a European Research Council (ERC) Advanced Investigator Grant (TelMetab) and Wellcome Trust Senior Investigator and Collaborative Grants. Aguilera lab work is supported by grants from the Spanish Ministry of Economy and Competitiveness (BFU2016-75058-P), European Research Council(ERC) Advanced Investigator Grant (ERC2014 AdG669898 TARLOOP), and the European Union (FEDER). T.G.-M. was holder of postdoctoral grants from the CSICJAE-Doc and the Junta de Andalucía Excellence Program (CVI-4567).Elsevier BVCancer Research UKMedical Research Council (UK)Wellcome TrustEuropean CommissionMinisterio de Economía y Competitividad (España)Consejo Superior de Investigaciones Científicas (España)Junta de AndalucíaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2020202020192020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/202497reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2016-75058-Phttp://dx.doi.org/10.1016/j.celrep.2018.12.074Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2024972026-05-22T06:33:51Z
dc.title.none.fl_str_mv A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs
title A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs
spellingShingle A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs
García-Muse, Tatiana
Meiosis
DNA damage response
ATR/ATM
DNA double-strand breaks
Synaptonemal complex
Inter-sister repair
BRC-1
title_short A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs
title_full A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs
title_fullStr A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs
title_full_unstemmed A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs
title_sort A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs
dc.creator.none.fl_str_mv García-Muse, Tatiana
Galindo-Díaz, Ulises
García-Rubio, María L.
Martin, Julie S.
Polanowska, Jolanta
O'Reilly, Nicola J.
Aguilera, Andrés
Boulton, Simon J.
author García-Muse, Tatiana
author_facet García-Muse, Tatiana
Galindo-Díaz, Ulises
García-Rubio, María L.
Martin, Julie S.
Polanowska, Jolanta
O'Reilly, Nicola J.
Aguilera, Andrés
Boulton, Simon J.
author_role author
author2 Galindo-Díaz, Ulises
García-Rubio, María L.
Martin, Julie S.
Polanowska, Jolanta
O'Reilly, Nicola J.
Aguilera, Andrés
Boulton, Simon J.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Cancer Research UK
Medical Research Council (UK)
Wellcome Trust
European Commission
Ministerio de Economía y Competitividad (España)
Consejo Superior de Investigaciones Científicas (España)
Junta de Andalucía
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Meiosis
DNA damage response
ATR/ATM
DNA double-strand breaks
Synaptonemal complex
Inter-sister repair
BRC-1
topic Meiosis
DNA damage response
ATR/ATM
DNA double-strand breaks
Synaptonemal complex
Inter-sister repair
BRC-1
description Garcia-Muse et al. show that the checkpoint kinases ATM and ATR respond to excessive or unrepaired meiotic DSBs by phosphorylating the core synaptonemal complex, which channels repair via the sister chromatid. These findings reveal a mechanism that switches repair partner bias to protect meiotic cells from unscheduled DNA breaks.Accurate meiotic chromosome segregation critically depends on the formation of inter-homolog crossovers initiated by double-strand breaks (DSBs). Inaccuracies in this process can drive aneuploidy and developmental defects, but how meiotic cells are protected from unscheduled DNA breaks remains unexplored. Here we define a checkpoint response to persistent meiotic DSBs in C. elegans that phosphorylates the synaptonemal complex (SC) to switch repair partner from the homolog to the sister chromatid. A key target of this response is the core SC component SYP-1, which is phosphorylated in response to ionizing radiation (IR) or unrepaired meiotic DSBs. Failure to phosphorylate (syp-1) or dephosphorylate (syp-1) SYP-1 in response to DNA damage results in chromosome non-dysjunction, hyper-sensitivity to IR-induced DSBs, and synthetic lethality with loss of brc-1. Since BRC-1 is required for inter-sister repair, these observations reveal that checkpoint-dependent SYP-1 phosphorylation safeguards the germline against persistent meiotic DSBs by channelling repair to the sister chromatid.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/202497
url http://hdl.handle.net/10261/202497
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2016-75058-P
http://dx.doi.org/10.1016/j.celrep.2018.12.074
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier BV
publisher.none.fl_str_mv Elsevier BV
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869420999302184960
score 15,812429

Similares en LA Referencia