Inhibition of REV3 expression induces persistent DNA damage and growth arrest in cancer cells.

ABSTRACT: REV3 is the catalytic subunit of DNA translesion synthesis polymerase ζ. Inhibition of REV3 expression increases the sensitivity of human cells to a variety of DNA-damaging agents and reduces the formation of resistant cells. Surprisingly, we found that short hairpin RNA-mediated depletion of REV3 per se suppresses colony formation of lung (A549, Calu-3), breast (MCF-7, MDA-MB-231), mesothelioma (IL45 and ZL55), and colon (HCT116 +/-p53) tumor cell lines, whereas control cell lines (AD293, LP9-hTERT) and the normal mesothelial primary culture (SDM104) are less affected. Inhibition of REV3 expression in cancer cells leads to an accumulation of persistent DNA damage as indicated by an increase in phospho-ATM, 53BP1, and phospho-H2AX foci formation, subsequently leading to the activation of t

SUBMITTER: Knobel PA 

PROVIDER: S-EPMC3201572 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature