Chromosomal integrity after UV irradiation requires FANCD2-mediated repair of double strand breaks

Fanconi Anemia (FA) is a rare autosomal recessive disorder characterized by hypersensitivity to inter-strand crosslinks (ICLs). FANCD2, a central factor of the FA pathway, is essential for the repair of double strand breaks (DSBs) generated during fork collapse at ICLs. While lesions different from...

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Detalhes bibliográficos
Autores: Federico, Maria Belén, Vallerga, María, Radl, Daniela Betiana, Paviolo, Natalia Soledad, Bocco, Jose Luis, Di Giorgio, Marina, Soria, Gastón, Gottifredi, Vanesa
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/46486
Acesso em linha:http://hdl.handle.net/11336/46486
Access Level:acceso abierto
Palavra-chave:DNA DAMAGE RESPONSE
FANCONI ANEMIA
FANCD2
CHROMOSOMAL STABILITY
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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oai_identifier_str oai:ri.conicet.gov.ar:11336/46486
network_acronym_str AR
network_name_str Argentina
repository_id_str
dc.title.none.fl_str_mv Chromosomal integrity after UV irradiation requires FANCD2-mediated repair of double strand breaks
title Chromosomal integrity after UV irradiation requires FANCD2-mediated repair of double strand breaks
spellingShingle Chromosomal integrity after UV irradiation requires FANCD2-mediated repair of double strand breaks
Federico, Maria Belén
DNA DAMAGE RESPONSE
FANCONI ANEMIA
FANCD2
CHROMOSOMAL STABILITY
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
title_short Chromosomal integrity after UV irradiation requires FANCD2-mediated repair of double strand breaks
title_full Chromosomal integrity after UV irradiation requires FANCD2-mediated repair of double strand breaks
title_fullStr Chromosomal integrity after UV irradiation requires FANCD2-mediated repair of double strand breaks
title_full_unstemmed Chromosomal integrity after UV irradiation requires FANCD2-mediated repair of double strand breaks
title_sort Chromosomal integrity after UV irradiation requires FANCD2-mediated repair of double strand breaks
dc.creator.none.fl_str_mv Federico, Maria Belén
Vallerga, María
Radl, Daniela Betiana
Paviolo, Natalia Soledad
Bocco, Jose Luis
Di Giorgio, Marina
Soria, Gastón
Gottifredi, Vanesa
author Federico, Maria Belén
author_facet Federico, Maria Belén
Vallerga, María
Radl, Daniela Betiana
Paviolo, Natalia Soledad
Bocco, Jose Luis
Di Giorgio, Marina
Soria, Gastón
Gottifredi, Vanesa
author_role author
author2 Vallerga, María
Radl, Daniela Betiana
Paviolo, Natalia Soledad
Bocco, Jose Luis
Di Giorgio, Marina
Soria, Gastón
Gottifredi, Vanesa
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DNA DAMAGE RESPONSE
FANCONI ANEMIA
FANCD2
CHROMOSOMAL STABILITY
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
topic DNA DAMAGE RESPONSE
FANCONI ANEMIA
FANCD2
CHROMOSOMAL STABILITY
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
description Fanconi Anemia (FA) is a rare autosomal recessive disorder characterized by hypersensitivity to inter-strand crosslinks (ICLs). FANCD2, a central factor of the FA pathway, is essential for the repair of double strand breaks (DSBs) generated during fork collapse at ICLs. While lesions different from ICLs can also trigger fork collapse, the contribution of FANCD2 to the resolution of replication-coupled DSBs generated independently from ICLs is unknown. Intriguingly, FANCD2 is readily activated after UV irradiation, a DNA-damaging agent that generates predominantly intra-strand crosslinks but not ICLs. Hence, UV irradiation is an ideal tool to explore the contribution of FANCD2 to the DNA damage response triggered by DNA lesions other than ICL repair. Here we show that, in contrast to ICL-causing agents, UV radiation compromises cell survival independently from FANCD2. In agreement, FANCD2 depletion does not increase the amount of DSBs generated during the replication of UV-damaged DNA and is dispensable for UV-induced checkpoint activation. Remarkably however, FANCD2 protects UV-dependent, replication-coupled DSBs from aberrant processing by non-homologous end joining, preventing the accumulation of micronuclei and chromatid aberrations including non-homologous chromatid exchanges. Hence, while dispensable for cell survival, FANCD2 selectively safeguards chromosomal stability after UV-triggered replication stress.
publishDate 2016
dc.date.none.fl_str_mv 2016-01-14
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/46486
Federico, Maria Belén; Vallerga, María ; Radl, Daniela Betiana; Paviolo, Natalia Soledad; Bocco, Jose Luis; et al.; Chromosomal integrity after UV irradiation requires FANCD2-mediated repair of double strand breaks; Public Library of Science; Plos Genetics; 14-1-2016
1553-7390
1553-7404
CONICET Digital
CONICET
url http://hdl.handle.net/11336/46486
identifier_str_mv Federico, Maria Belén; Vallerga, María ; Radl, Daniela Betiana; Paviolo, Natalia Soledad; Bocco, Jose Luis; et al.; Chromosomal integrity after UV irradiation requires FANCD2-mediated repair of double strand breaks; Public Library of Science; Plos Genetics; 14-1-2016
1553-7390
1553-7404
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pgen.1005792
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005792
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1799195547622440960
spelling Chromosomal integrity after UV irradiation requires FANCD2-mediated repair of double strand breaksFederico, Maria BelénVallerga, MaríaRadl, Daniela BetianaPaviolo, Natalia SoledadBocco, Jose LuisDi Giorgio, MarinaSoria, GastónGottifredi, VanesaDNA DAMAGE RESPONSEFANCONI ANEMIAFANCD2CHROMOSOMAL STABILITYhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Fanconi Anemia (FA) is a rare autosomal recessive disorder characterized by hypersensitivity to inter-strand crosslinks (ICLs). FANCD2, a central factor of the FA pathway, is essential for the repair of double strand breaks (DSBs) generated during fork collapse at ICLs. While lesions different from ICLs can also trigger fork collapse, the contribution of FANCD2 to the resolution of replication-coupled DSBs generated independently from ICLs is unknown. Intriguingly, FANCD2 is readily activated after UV irradiation, a DNA-damaging agent that generates predominantly intra-strand crosslinks but not ICLs. Hence, UV irradiation is an ideal tool to explore the contribution of FANCD2 to the DNA damage response triggered by DNA lesions other than ICL repair. Here we show that, in contrast to ICL-causing agents, UV radiation compromises cell survival independently from FANCD2. In agreement, FANCD2 depletion does not increase the amount of DSBs generated during the replication of UV-damaged DNA and is dispensable for UV-induced checkpoint activation. Remarkably however, FANCD2 protects UV-dependent, replication-coupled DSBs from aberrant processing by non-homologous end joining, preventing the accumulation of micronuclei and chromatid aberrations including non-homologous chromatid exchanges. Hence, while dispensable for cell survival, FANCD2 selectively safeguards chromosomal stability after UV-triggered replication stress.Fil: Federico, Maria Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Vallerga, María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Radl, Daniela Betiana. Autoridad Regulatoria Nuclear; ArgentinaFil: Paviolo, Natalia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Bocco, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Di Giorgio, Marina. Autoridad Regulatoria Nuclear; ArgentinaFil: Soria, Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Gottifredi, Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaPublic Library of Science2016-01-14info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/46486Federico, Maria Belén; Vallerga, María ; Radl, Daniela Betiana; Paviolo, Natalia Soledad; Bocco, Jose Luis; et al.; Chromosomal integrity after UV irradiation requires FANCD2-mediated repair of double strand breaks; Public Library of Science; Plos Genetics; 14-1-20161553-73901553-7404CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pgen.1005792info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005792info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T13:55:52Zoai:ri.conicet.gov.ar:11336/46486instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 13:55:53.067CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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