Transcriptional regulation by Asf1: new mechanistic insights from studies of the DNA damage response to replication stress.

ABSTRACT: Asf1 is a conserved histone H3/H4 chaperone. We find that Asf1 in budding yeast promotes an essential cellular response to replication stress caused by the ribonucleotide reductase inhibitor hydroxyurea. That is, Asf1 stimulates derepression of DNA damage response (DDR) genes during the S phase. Derepression of DDR genes strongly correlates with Asf1 binding to their promoters. Having identified the C terminus and histone-binding domains of Asf1 as molecular determinants of its constitutive and inducible association with chromatin, we tested whether Asf1 binding to DDR genes is mechanistically important for their derepression. Our results provide little support for this hypothesis. Rather, the contribution of Asf1 to DDR gene derepression depends on its ability to stimulate H3K56 acetylati

SUBMITTER: Minard LV 

PROVIDER: S-EPMC3044965 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature