DNA lesions trigger DNA damage checkpoint (DDC) signaling which arrests cell cycle progression and promotes DNA damage repair. In Saccharomyces cerevisiae, phosphorylation of histone H2A (gammaH2A, equivalent to gammaH2AX in mammals) is an early chromatin mark induced by DNA damage that is recognized by a group of DDC and DNA repair factors. We find that gammaH2A negatively regulates the G2/M checkpoint in response to the genotoxin camptothecin, which is a DNA topoisomerase I poison. gammaH2A also suppresses DDC signaling induced by the DNA alkylating agent methyl methanesulfonate. These results differ from prior findings, which demonstrate positive or no roles of gammaH2A in DDC in response to other DNA damaging agents such as phleomycin and ionizing radiation, which suggest that gammaH2A has DNA damage-specific effects on DDC signaling. We also find evidence supporting the notion that gammaH2A regulates DDC signaling by mediating the competitive recruitment of the DDC mediator Rad9 and the DNA repair factor Rtt107 to DNA lesions. We propose that gammaH2A/gammaH2AX serves to create a dynamic balance between DDC and DNA repair that is influenced by the nature of DNA damage.

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Journal Article

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Siler J, Guo N, Liu Z, Qin Y, Bi X

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