Silent repair accounts for cell cycle specificity in the signaling of oxidative DNA lesions

Reactive oxygen species are the most important source of DNA lesions in aer obic organisms, but little is known about the activation of the DNA checkpo ints in response to oxidative stress. We show that treatment of yeast cells with sublethal concentrations of hydrogen peroxide induces a Mec1-dependen t phosphorylation of Rad53 and a Rad53-dependent cell cycle delay specifica lly during S phase. The lack of Rad53 phosphorylation after hydrogen peroxi de treatment in the G(1) and G(2) phases is due to the silent repair of oxi dative DNA lesions produced at these stages by the base excision repair (BE R) pathway. Only the disruption of the BER pathway and the accumulation and /or treatment of DNA intermediates by alternative repair pathways reveal th e existence of primary DNA lesions induced at all phases of the cell cycle by hydrogen peroxide. Our data illustrate both the concept of silent repair of DNA damage and the high sensitivity of S-phase cells to hydrogen peroxi de.