TY - JOUR
T1 - Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells
AU - Lerner, Leticia K.
AU - Francisco, Guilherme
AU - Soltys, Daniela T.
AU - Rocha, Clarissa R.R.
AU - Quinet, Annabel
AU - Vessoni, Alexandre T.
AU - Castro, Ligia P.
AU - David, Taynah I.P.
AU - Bustos, Silvina O.
AU - Strauss, Bryan E.
AU - Gottifredi, Vanesa
AU - Stary, Anne
AU - Sarasin, Alain
AU - Chammas, Roger
AU - Menck, Carlos F.M.
N1 - Funding Information:
Fundac¸ão de Amparo à Pesquisa do Estado de São Paulo (FAPESP, São Paulo, Brazil) [2014/15982-6 and 2013/21075-9]; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brasília, DF, Brazil); Coordenac¸ão de Aperfeic¸oamento de Pessoal de Nível Superior (CAPES, Brasília, DF, Brazil); Centre Nationale de Recherche Scientifique (CNRS, France). Funding for open access charge: Fundac¸ão de Amparo à Pesquisa do Estado de São Paulo (FAPESP, São Paulo, Brazil) to CFM Menck. Conflict of interest statement. None declared.
Publisher Copyright:
© The Author(s) 2016.
PY - 2017/2/17
Y1 - 2017/2/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85020320607&partnerID=8YFLogxK
U2 - 10.1093/nar/gkw1196
DO - 10.1093/nar/gkw1196
M3 - Article
C2 - 28180309
AN - SCOPUS:85020320607
SN - 0305-1048
VL - 45
SP - 1270
EP - 1280
JO - Nucleic acids research
JF - Nucleic acids research
IS - 3
ER -