Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells
| Autor: | Ligia Pereira Castro, Vanesa Gottifredi, Alain Sarasin, Alexandre T. Vessoni, Guilherme Francisco, Silvina Odete Bustos, Annabel Quinet, Daniela T. Soltys, Roger Chammas, Taynah I.P. David, Leticia K. Lerner, Bryan E. Strauss, Carlos Frederico Martins Menck, Anne Stary, Clarissa Ribeiro Reily Rocha |
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| Přispěvatelé: | University of São Paulo (USP), Instituto do Câncer do Estado = Cancer Institute of the State of São Paulo (ICESP), Institute of Chemistry [University of São Paulo] | Instituto de Química [Universidade de São Paulo], Fundación Instituto Leloir [Buenos Aires], Intégrité du génome et cancers (IGC), Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
p53 DNA Repair MESH: DNA Replication DNA polymerase eta DNA-Directed DNA Polymerase Genome Integrity Repair and Replication purl.org/becyt/ford/1 [https] 0302 clinical medicine FIBROBLASTOS MESH: DNA-Directed DNA Polymerase SOS response MESH: Tumor Suppressor Protein p53 Polymerase MESH: DNA Repair biology MESH: DNA Cell cycle MESH: Gene Expression Regulation Chromatin TRANLESION DNA SYNTHESIS MESH: Cell Survival 030220 oncology & carcinogenesis CIENCIAS NATURALES Y EXACTAS DNA Replication DNA damage Cell Survival Ultraviolet Rays Otras Ciencias Biológicas [SDV.CAN]Life Sciences [q-bio]/Cancer [SDV.BC]Life Sciences [q-bio]/Cellular Biology Cell Line MESH: Chromatin Ciencias Biológicas 03 medical and health sciences parasitic diseases MESH: Dose-Response Relationship Radiation Genetics Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology purl.org/becyt/ford/1.6 [https] MESH: Humans DNA synthesis Dose-Response Relationship Radiation DNA SOS RESPONSE Fibroblasts Molecular biology MESH: Cell Line 030104 developmental biology Gene Expression Regulation MESH: Fibroblasts biology.protein MESH: Ultraviolet Rays Tumor Suppressor Protein p53 Nucleotide excision repair |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Nucleic Acids Research Nucleic Acids Research, Oxford University Press, 2017, 45 (3), pp.1270-1280. ⟨10.1093/nar/gkw1196⟩ CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| ISSN: | 0305-1048 1362-4962 |
| DOI: | 10.1093/nar/gkw1196⟩ |
| Popis: | Genome lesions trigger biological responses that help cells manage damaged DNA, improving cell survival. Pol eta is a translesion synthesis (TLS) polymerase that bypasses lesions that block replicative polymerases, avoiding continued stalling of replication forks, which could lead to cell death. p53 also plays an important role in preventing cell death after ultraviolet (UV) light exposure. Intriguingly, we show that p53 does so by favoring translesion DNA synthesis by pol eta. In fact, the p53-dependent induction of pol eta in normal and DNA repair-deficient XP-C human cells after UV exposure has a protective effect on cell survival after challenging UV exposures, which was absent in p53- and Pol H-silenced cells. Viability increase was associated with improved elongation of nascent DNA, indicating the protective effect was due to more efficient lesion bypass by pol eta. This protection was observed in cells proficient or deficient in nucleotide excision repair, suggesting that, from a cell survival perspective, proper bypass of DNA damage can be as relevant as removal. These results indicate p53 controls the induction of pol eta in DNA damaged human cells, resulting in improved TLS and enhancing cell tolerance to DNA damage, which parallels SOS responses in bacteria. Fil: Lerner, Leticia K.. Universidade de Sao Paulo; Brasil Fil: Francisco, Guilherme. Cancer Institute Of The State Of Sao Paulo; Brasil Fil: Soltys, Daniela T.. Universidade de Sao Paulo; Brasil Fil: Rocha, Clarissa R.R.. Universidade de Sao Paulo; Brasil Fil: Quinet, Annabel. Universidade de Sao Paulo; Brasil Fil: Vessoni, Alexandre T.. Universidade de Sao Paulo; Brasil Fil: Castro, Ligia P.. Universidade de Sao Paulo; Brasil Fil: David, Taynah I.P.. Universidade de Sao Paulo; Brasil Fil: Bustos, Silvina O.. Cancer Institute Of The State Of Sao Paulo; Brasil Fil: Strauss, Bryan E.. Universidade de Sao Paulo; Brasil 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. Fundación Instituto Leloir; Argentina Fil: Stary, Anne. Centre National de la Recherche Scientifique; Francia Fil: Sarasin, Alain. Centre National de la Recherche Scientifique; Francia Fil: Chammas, Roger. Cancer Institute Of The State Of São Paulo; Brasil Fil: Menck, Carlos F.M.. Universidade de Sao Paulo; Brasil |
| Databáze: | OpenAIRE |
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