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

Maria Carolina S. Moraes, Annabel Quinet de Andrade, Helotonio Carvalho, Temenouga Guecheva, Mateus H. Agnoletto, João A.P. Henriques, Alain Sarasin, Anne Stary, Jenifer Saffi, Carlos F.M. Menck

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish
Pages (from-to)108-118
Number of pages11
JournalCancer Letters
Volume314
Issue number1
DOIs
StatePublished - Jan 1 2012

Keywords

  • DNA polymerase eta (pol eta)
  • DNA repair
  • Doxorubicin
  • LY294002
  • XPA
  • XPV

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