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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells

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Autor(es):
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Lerner, Leticia K. ; Francisco, Guilherme ; Soltys, Daniela T. ; Rocha, Clarissa R. R. ; Quinet, Annabel ; Vessoni, Alexandre T. ; Castro, Ligia P. ; David, Taynah I. P. ; Bustos, Silvina O. ; Strauss, Bryan E. ; Gottifredi, Vanesa ; Stary, Anne ; Sarasin, Alain ; Chammas, Roger ; Menck, Carlos F. M.
Número total de Autores: 15
Tipo de documento: Artigo Científico
Fonte: Nucleic Acids Research; v. 45, n. 3, p. 1270-1280, FEB 2017.
Citações Web of Science: 11
Resumo

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 afterUV 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. (AU)

Processo FAPESP: 13/21075-9 - Participação da NADPH oxidase 2 induzida pelo estrogênio em lesões no DNA e na regulação da autofagia em linhagem celular de mama
Beneficiário:Carlos Frederico Martins Menck
Linha de fomento: Auxílio à Pesquisa - Pesquisador Visitante - Brasil
Processo FAPESP: 14/15982-6 - Consequências de deficiências de reparo de lesões no genoma
Beneficiário:Carlos Frederico Martins Menck
Linha de fomento: Auxílio à Pesquisa - Temático