Yeast histone 2a serine 129 is essential for the efficient repair of checkpoint-blind dna damage
Redon, Christophe Pilch, Duane R. Rogakou, Emmy P. Orr, Ann H. Lowndes, Noel F. Bonner, William M.
Redon, Christophe
Pilch, Duane R.
Rogakou, Emmy P.
Orr, Ann H.
Lowndes, Noel F.
Bonner, William M.
Publication Date
2003-06-06
Type
Article
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Citation
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
Abstract
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.
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Wiley-Blackwell
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Attribution-NonCommercial-NoDerivs 3.0 Ireland