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Redon, C,Pilch, DR,Rogakou, EP,Orr, AH,Lowndes, NF,Bonner, WM
2003
July
Embo Reports
Yeast histone 2A serine 129 is essential for the efficient repair of checkpoint-blind DNA damage
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DOUBLE-STRAND BREAKS CELL-CYCLE TOPOISOMERASE-I REPLICATION H2AX PATHWAY RAD53 ATM
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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.
DOI 10.1038/sj.embor.embor871
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