Both XPA and DNA polymerase eta are necessary for the repair of doxorubicin-induced DNA lesions

Both XPA and DNA polymerase eta are necessary for the repair of doxorubicin-induced DNA lesions

Author Moraes, Maria Carolina S. Google Scholar
Andrade, Annabel Quinet de Google Scholar
Carvalho, Helotonio Autor UNIFESP Google Scholar
Guecheva, Temenouga Google Scholar
Agnoletto, Mateus H. Google Scholar
Henriques, Joao A. P. Google Scholar
Sarasin, Alain Google Scholar
Stary, Anne Google Scholar
Saffi, Jenifer Google Scholar
Menck, Carlos F. M. Google Scholar
Institution Universidade de São Paulo (USP)
Univ Paris Sud
Universidade Federal de São Paulo (UNIFESP)
Univ Fed Rio Grande do Sul
Fed Univ Hlth Sci Porto Alegre UFCSPA
Abstract Doxorubicin (DOX) is an important tumor chemotherapeutic agent, acting mainly by genotoxic action. This work focus on cell processes that help cell survival, after DOX-induced DNA damage. in fact, cells deficient for XPA or DNA polymerase eta (pol eta, XPV) proteins (involved in distinct DNA repair pathways) are highly DOX-sensitive. Moreover, LY294002, an inhibitor of PIKK kinases, showed a synergistic killing effect in cells deficient in these proteins, with a strong induction of G2/M cell cycle arrest. Taken together, these results indicate that XPA and pol eta proteins participate in cell resistance to DOX-treatment, and kinase inhibitors can selectively enhance its killing effects, probably reducing the cell ability to recover from breaks induced in DNA. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
Keywords Doxorubicin
DNA polymerase eta (pol eta)
XPV
XPA
LY294002
DNA repair
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
USP-COFECUB (São Paulo, Brazil)
Date 2012-01-01
Published in Cancer Letters. Clare: Elsevier B.V., v. 314, n. 1, p. 108-118, 2012.
ISSN 0304-3835 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 108-118
Origin http://dx.doi.org/10.1016/j.canlet.2011.09.019
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000298531900012
URI http://repositorio.unifesp.br/handle/11600/34339

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