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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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.
Total Authors: 15
Document type: Journal article
Source: Nucleic Acids Research; v. 45, n. 3, p. 1270-1280, FEB 2017.
Web of Science Citations: 11

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)

FAPESP's process: 13/21075-9 - Participation of NADPH oxidase 2 induced by estrogen in the formation of DNA damage and autophagy regulation in breast cells
Grantee:Carlos Frederico Martins Menck
Support type: Research Grants - Visiting Researcher Grant - Brazil
FAPESP's process: 14/15982-6 - Consequences of repair deficiencies in damaged genome
Grantee:Carlos Frederico Martins Menck
Support type: Research Projects - Thematic Grants