The amino-terminal tails of histones H2A and H3 coordinate efficient base excision repair, DNA damage signaling and postreplication repair in Saccharomyces cerevisiae.
Bottom Line: Combinatorial deletions reveal that the H2A and H3 N-tails are important for the removal of MMS-induced DNA lesions due to their role in regulating the basal and MMS-induced expression of DNA glycosylase Mag1.We further show that the H3 N-tail functions in the Rad9/Rad53 DNA damage signaling pathway, but this function does not appear to be the primary cause of MMS sensitivity of the double tailless mutants.We observed increased levels of ubiquitylated PCNA and significantly lower mutation frequency in the tailless H2A/H3 mutant, indicating a defect in postreplication repair.
Affiliation: School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520, USA.Show MeSH
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Mentions: We performed epistasis studies to genetically identify which DNA damage response pathways are important for the MMS sensitivity of the tH2A:tH3 mutant. First, we tested epistasis for the BER pathway by examining double mutants in which the MAG1 gene was deleted in the tH2A, tH3, and tH2A:tH3 mutant strains. As shown in Figure 6A.ii, the deletion of MAG1 with any of the tail deletion combinations showed increased MMS sensitivity over that of the mag1Δ mutant alone, indicating that histone tailless mutants are not epistatic to the BER pathway. These data confirm that BER is not the only MMS-response pathway affected when the N-tails of H2A and H3 are deleted.
Affiliation: School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520, USA.