DNA Double-Strand Break Repair

ownloade C regulates a myriad of genes controlling cell proliferation, metabolism, differentiation, and apoptosis. lso controls the expression of DNA double-strand break (DSB) repair genes and therefore may be a ial target for anticancer therapy to sensitize cancer cells to DNA damage or prevent genetic instability. report, we studied whether MYC binds to DSB repair gene promoters and modulates cell survival onse to DNA-damaging agents. Chromatin immunoprecipitation studies showed that MYC associates everal DSB repair gene promoters including Rad51, Rad51B, Rad51C, XRCC2, Rad50, BRCA1, BRCA2, Kcs, XRCC4, Ku70, and DNA ligase IV. Endogenous MYC protein expression was associated with sed RAD51 and KU70 protein expression of a panel of cancer cell lines of varying histopathology. Inducf MYC in G0-G1 and S-G2-M cells resulted in upregulation of Rad51 gene expression. MYC knockdown small interfering RNA (siRNA) led to decreased RAD51 expression but minimal effects on homologous bination based on a flow cytometry direct repeat green fluorescent protein assay. siRNA to MYC d in tumor cell kill in DU145 and H1299 cell lines in a manner independent of apoptosis. However, ependent changes in DSB repair protein expression were not sufficient to sensitize cells to mitomycin onizing radiation, two agents selectively toxic to DSB repair–deficient cells. Our results suggest that C or i anti-MYC agents may target cells to prevent genetic instability but would not lead to differential radiosensitization or chemosensitization. Cancer Res; 70(21); 8748–59. ©2010 AACR.