TY - JOUR
T1 - Both XPA and DNA polymerase eta are necessary for the repair of doxorubicin-induced DNA lesions
AU - Moraes, Maria Carolina S.
AU - de Andrade, Annabel Quinet
AU - Carvalho, Helotonio
AU - Guecheva, Temenouga
AU - Agnoletto, Mateus H.
AU - Henriques, João A.P.
AU - Sarasin, Alain
AU - Stary, Anne
AU - Saffi, Jenifer
AU - Menck, Carlos F.M.
N1 - Funding Information:
M.C.S. Moraes has a post-doctoral fellowship from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, São Paulo, Brazil). This research was supported by FAPESP (São Paulo, Brazil), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brasília, Brazil) and USP-COFECUB (São Paulo, Brazil).
PY - 2012/1/1
Y1 - 2012/1/1
N2 - 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.
AB - 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.
KW - DNA polymerase eta (pol eta)
KW - DNA repair
KW - Doxorubicin
KW - LY294002
KW - XPA
KW - XPV
UR - https://www.scopus.com/pages/publications/82355191713
U2 - 10.1016/j.canlet.2011.09.019
DO - 10.1016/j.canlet.2011.09.019
M3 - Article
C2 - 21999933
AN - SCOPUS:82355191713
SN - 0304-3835
VL - 314
SP - 108
EP - 118
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -