SIRT1 inhibition impairs non-homologous end joining DNA damage repair by increasing Ku70 acetylation in chronic myeloid leukemia cells.

ABSTRACT: Most chemotherapeutic agents for leukemia are DNA damaging agents. However, DNA lesions can be repaired by activities of DNA repair systems. Increasing evidence have shown that enhanced DNA damage repair capacity contributes to chemotherapy resistance in leukemia cells. Thus, targeting DNA repair mechanisms is a promising strategy for novel leukemia treatment. SIRT1 expressions were downregulated by lentivirus-delivered SIRT1 shRNA in myeloid leukemia cells. SIRT1 mRNA and protein levels were analyzed by real-time PCR and Western blot, respectively. Flow cytometry was carried out to analyze cell cycle progression, apoptosis and DNA damage repair efficiency. DNA damage levels were assessed by alkaline comet assay, and H2AX phosphorylation was analyzed by immunoblotting and immunofluorescenc

SUBMITTER: Zhang W 

PROVIDER: S-EPMC4924659 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature