Yeast histone 2a serine 129 is essential for the efficient repair of checkpoint-blind dna damage
Pilch, Duane R.
Rogakou, Emmy P.
Orr, Ann H.
Lowndes, Noel F.
Bonner, William M.
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Redon, Christophe; Pilch, Duane R. Rogakou, Emmy P.; Orr, Ann H.; Lowndes, Noel F.; Bonner, William M. (2003). Yeast histone 2a serine 129 is essential for the efficient repair of checkpoint-blind dna damage. EMBO Reports 4 (7), 678-684
Cells maintain genomic stability by the coordination of DNA-damage repair and cell-cycle checkpoint control. In replicating cells, DNA damage usually activates intra-S-phase checkpoint controls, which are characterized by delayed S-phase progression and increased Rad53 phosphorylation. We show that in budding yeast, the intra-S-phase checkpoint controls, although functional, are not activated by the topoisomerase I inhibitor camptothecin (CPT). In a CPT-hypersensitive mutant strain that lacks the histone 2A (H2A) phosphatidylinositol-3-OH kinase (PI(3) K) motif at Ser 129 (h2a-s129a), the hypersensitivity was found to result from a failure to process full-length chromosomal DNA molecules during ongoing replication. H2A Ser 129 is not epistatic to the RAD24 and RAD9 checkpoint genes, suggesting a non-checkpoint role for the H2A PI(3) K site. These results suggest that H2A Ser 129 is an essential component for the efficient repair of DNA double-stranded breaks (DSBs) during replication in yeast, particularly of those DSBs that do not induce the intra-S-phase checkpoint.