dc.contributor.author | Piberger, Ann Liza | |
dc.contributor.author | Bowry, Akhil | |
dc.contributor.author | Kelly, Richard D W | |
dc.contributor.author | Walker, Alexandra K | |
dc.contributor.author | Gonzalez-Acosta, Daniel | |
dc.contributor.author | Bailey, Laura J | |
dc.contributor.author | Doherty, Aidan J | |
dc.contributor.author | Méndez, Juan | |
dc.contributor.author | Morris, Joanna R | |
dc.contributor.author | Bryant, Helen E | |
dc.contributor.author | Petermann, Eva | |
dc.contributor.author | Mendez, Juan | |
dc.date.accessioned | 2021-03-09T14:23:07Z | |
dc.date.available | 2021-03-09T14:23:07Z | |
dc.date.issued | 2020-11-11 | |
dc.identifier.citation | Nat Commun.2020 ;11(1):5863. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/12177 | |
dc.description.abstract | Stalled replication forks can be restarted and repaired by RAD51-mediated homologous recombination (HR), but HR can also perform post-replicative repair after bypass of the obstacle. Bulky DNA adducts are important replication-blocking lesions, but it is unknown whether they activate HR at stalled forks or behind ongoing forks. Using mainly BPDE-DNA adducts as model lesions, we show that HR induced by bulky adducts in mammalian cells predominantly occurs at post-replicative gaps formed by the DNA/RNA primase PrimPol. RAD51 recruitment under these conditions does not result from fork stalling, but rather occurs at gaps formed by PrimPol re-priming and resection by MRE11 and EXO1. In contrast, RAD51 loading at double-strand breaks does not require PrimPol. At bulky adducts, PrimPol promotes sister chromatid exchange and genetic recombination. Our data support that HR at bulky adducts in mammalian cells involves post-replicative gap repair and define a role for PrimPol in HR-mediated DNA damage tolerance. | es_ES |
dc.description.sponsorship | We thank Drs Rebecca M. Jones, Katarzyna Starowicz, and Karen Sisley for advice on PFGE and SCE quantification, and Dr. Ana Losada for the kind gift of anti-SMC1 antibody. This work was supported by the German Research Foundation Pl 1300/1-1 (A.L.P.), Medical Research Council MR/S021310/1 (A.L.P. and E.P.), Cancer Research UK C25526/A28275 and Cancer Research UK Birmingham Centre Award C17422/A25154 (E.P.), Cancer Research UK C8820/A19062 (A.K.W. and J.R.M.), Wellcome Trust 206343/Z/17/Z (J.R.M.), University of Sheffield 322149 (H.E.B.), Biotechnology and Biological Science Research Council BB/H019723/1 and BB/M008800/1 (A.J.D.), and the Spanish Ministry of Science and Innovation BFU2016-80402-R, co-financed by E.U. ERDF funds (J.M.). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing Group | es_ES |
dc.type.hasVersion | SMUR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject.mesh | 4-Nitroquinoline-1-oxide | es_ES |
dc.subject.mesh | 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide | es_ES |
dc.subject.mesh | Benz(a)Anthracenes | es_ES |
dc.subject.mesh | Cell Line | es_ES |
dc.subject.mesh | DNA Adducts | es_ES |
dc.subject.mesh | DNA Primase | es_ES |
dc.subject.mesh | DNA, Single-Stranded | es_ES |
dc.subject.mesh | DNA-Directed DNA Polymerase | es_ES |
dc.subject.mesh | Homologous Recombination | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Multifunctional Enzymes | es_ES |
dc.subject.mesh | Quinolones | es_ES |
dc.subject.mesh | Rad51 Recombinase | es_ES |
dc.subject.mesh | Single Molecule Imaging | es_ES |
dc.subject.mesh | Sister Chromatid Exchange | es_ES |
dc.title | PrimPol-dependent single-stranded gap formation mediates homologous recombination at bulky DNA adducts. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-NoComercial-CompartirIgual 4.0 Internacional | * |
dc.identifier.pubmedID | 33203852 | es_ES |
dc.format.volume | 11 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 5863 | es_ES |
dc.identifier.doi | 10.1038/s41467-020-19570-7 | es_ES |
dc.contributor.funder | Deutsche Forschungsgemeinschaft (Alemania) | |
dc.contributor.funder | UK Research and Innovation | |
dc.contributor.funder | Medical Research Council (Reino Unido) | |
dc.contributor.funder | Unión Europea. Comisión Europea | |
dc.contributor.funder | Cancer Research UK (Reino Unido) | |
dc.contributor.funder | Wellcome Trust | |
dc.description.peerreviewed | No | es_ES |
dc.identifier.e-issn | 2041-1723 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1038/s41467-020-19570-7. | es_ES |
dc.identifier.journal | Nature communications | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Grupos de investigación::Grupo de Replicación de ADN | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/BFU2016-80402-R | es_ES |
dc.rights.accessRights | open access | es_ES |