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dc.contributor.author Hampp, Stephanie
dc.contributor.author Kiessling, Tina
dc.contributor.author Buechle, Kerstin
dc.contributor.author Mansilla, Sabrina Florencia
dc.contributor.author Thomale, Jürgen
dc.contributor.author Rall, Melanie
dc.contributor.author Ahn, Jinwoo
dc.contributor.author Pospiech, Helmut
dc.contributor.author Gottifredi, Vanesa
dc.contributor.author Wiesmüller, Lisa
dc.date.available 2017-06-16T19:43:35Z
dc.date.issued 2016-07
dc.identifier.citation Hampp, Stephanie; Kiessling, Tina; Buechle, Kerstin; Mansilla, Sabrina Florencia; Thomale, Jürgen; et al.; DNA damage tolerance pathway involving DNA polymerase ι and the tumor suppressor p53 regulates DNA replication fork progression; National Academy Of Sciences; Proceedings Of The National Academy Of Sciences Of The United States Of America; 113; 30; 7-2016; 4311-4319
dc.identifier.issn 0027-8424
dc.identifier.uri http://hdl.handle.net/11336/18349
dc.description.abstract DNA damage tolerance facilitates the progression of replication forks that have encountered obstacles on the template strands. It involves either translesion DNA synthesis initiated by proliferating cell nuclear antigen monoubiquitination or less well-characterized fork reversal and template switch mechanisms. Herein, we characterize a novel tolerance pathway requiring the tumor suppressor p53, the translesion polymerase ι (POLι), the ubiquitin ligase Rad5-related helicase-like transcription factor (HLTF), and the SWI/SNF catalytic subunit (SNF2) translocase zinc finger ran-binding domain containing 3 (ZRANB3). This novel p53 activity is lost in the exonuclease-deficient but transcriptionally active p53(H115N) mutant. Wild-type p53, but not p53(H115N), associates with POLι in vivo. Strikingly, the concerted action of p53 and POLι decelerates nascent DNA elongation and promotes HLTF/ZRANB3-dependent recombination during unperturbed DNA replication. Particularly after cross-linker-induced replication stress, p53 and POLι also act together to promote meiotic recombination enzyme 11 (MRE11)-dependent accumulation of (phospho-)replication protein A (RPA)-coated ssDNA. These results implicate a direct role of p53 in the processing of replication forks encountering obstacles on the template strand. Our findings define an unprecedented function of p53 and POLι in the DNA damage response to endogenous or exogenous replication stress.
dc.format application/pdf
dc.language.iso eng
dc.publisher National Academy Of Sciences
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject DNA polymerase iota
dc.subject p53
dc.subject Fork progression
dc.subject DNA fibers
dc.subject.classification Bioquímica y Biología Molecular
dc.subject.classification Ciencias Biológicas
dc.subject.classification CIENCIAS NATURALES Y EXACTAS
dc.title DNA damage tolerance pathway involving DNA polymerase ι and the tumor suppressor p53 regulates DNA replication fork progression
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2017-06-12T21:00:27Z
dc.identifier.eissn 1091-6490
dc.journal.volume 113
dc.journal.number 30
dc.journal.pagination 4311-4319
dc.journal.pais Estados Unidos
dc.journal.ciudad Washington
dc.description.fil Fil: Hampp, Stephanie. Universitat Ulm; Alemania
dc.description.fil Fil: Kiessling, Tina. Universitat Ulm; Alemania
dc.description.fil Fil: Buechle, Kerstin. Universitat Ulm; Alemania
dc.description.fil Fil: Mansilla, Sabrina Florencia. 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; Argentina
dc.description.fil Fil: Thomale, Jürgen. Universitat Duisburg - Essen; Alemania
dc.description.fil Fil: Rall, Melanie. Universitat Ulm; Alemania
dc.description.fil Fil: Ahn, Jinwoo. Columbia University; Estados Unidos
dc.description.fil Fil: Pospiech, Helmut. Leibniz Institute on Aging–Fritz Lipmann Institute; Alemania. University of Oulu; Finlandia
dc.description.fil Fil: 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; Argentina
dc.description.fil Fil: Wiesmüller, Lisa. Universitat Ulm; Alemania
dc.journal.title Proceedings Of The National Academy Of Sciences Of The United States Of America
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/113/30/E4311.long
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1073/pnas.1605828113


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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)