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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
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Thomale, Jürgen
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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
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Fork Progression
dc.subject
Dna Fibers
dc.subject.classification
Bioquímica y Biología Molecular
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Ciencias Biológicas
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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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