A requirement for replication in activation of the ATR-dependent DNA damage checkpoint

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A requirement for replication in activation of the ATR-dependent DNA damage checkpoint

Publisher
Cold Spring Harbor Laboratory Press
Publication Date
Sep 15, 2002
Source
PMC
Keywords
Disciplines
  • Biology
License
Unknown

Abstract

Using the Xenopus egg extract system, we investigated the involvement of DNA replication in activation of the DNA damage checkpoint. We show here that DNA damage slows replication in a checkpoint-independent manner and is accompanied by replication-dependent recruitment of ATR and Rad1 to chromatin. We also find that the replication proteins RPA and Polα accumulate on chromatin following DNA damage. Finally, damage-induced Chk1 phosphorylation and checkpoint arrest are abrogated when replication is inhibited. These data indicate that replication is required for activation of the DNA damage checkpoint and suggest a unifying model for ATR activation by diverse lesions during S phase.

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