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

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.

FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Sao Paulo, Brazil)

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Brazil

FAPESP (Sao Paulo, Brazil)

FAPESP (Sao Paulo, Brazil)

CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brasilia, Brazil)

CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brasilia, Brazil)

USPCOFECUB (Sao Paulo, Brazil)

USP-COFECUB (Sao Paulo, Brazil)