title: Both XPA and DNA polymerase eta are necessary for the repair of doxorubicin-induced DNA lesions.
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.
authors: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors: Maria Carolina S
authors: MC
authors: Moraes
authors: Annabel Quinet
authors: AQ
authors: de Andrade
authors: Helotonio
authors: H
authors: Carvalho
authors: Temenouga
authors: T
authors: Guecheva
authors: Mateus H
authors: MH
authors: Agnoletto
authors: João A P
authors: JA
authors: Henriques
authors: Alain
authors: A
authors: Sarasin
authors: Anne
authors: A
authors: Stary
authors: Jenifer
authors: J
authors: Saffi
authors: Carlos F M
authors: CF
authors: Menck
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004249:DNA Damage; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000502:physiology*; D004317:Doxorubicin / Q000494:pharmacology*; D006657:Histones / Q000032:analysis; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D051760:Xeroderma Pigmentosum Group A Protein / Q000502:physiology*; D000099270:Y-Family DNA Polymerases
chemical_list: D000903:Antibiotics, Antineoplastic; D002867:Chromones; D004259:DNA-Directed DNA Polymerase; D004317:Doxorubicin; D006657:Histones; D009025:Morpholines; D051760:Xeroderma Pigmentosum Group A Protein; C468783:H2AX protein, human; C497314:XPA protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases