Sharp-1 modulates the cellular response to DNA damage

Abstract: DNA damage checkpoints are essential for maintenance of genome integrity. We report here that inducible overexpression of the transcription factor Sharp-1 results in an S and G2/M cell cycle arrest, concomitant with the upregulation of Brca1 and GADD45α expression. In addition, we show that endogenous Sharp-1 mRNA is increased by DNA-damaging agents. Consistently, Sharp-1 overexpressing cells exhibit reduced apoptosis in response to chemotherapeutic drugs along with lower p53 expression and activity. Our studies identify a novel function for Sharp-1 in cell cycle arrest and DNA damage-induced apoptosis. Inappropriate Sharp-1 expression may therefore be associated with tumorigenesis. [Copyright &y& Elsevier]