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

Authors:
  • TBTony Byun
    Tony Byun
  • MYMuh-Ching Yee
    Muh-Ching Yee
  • MHMohammad Hekmat-Nejad
    Mohammad Hekmat-Nejad
  • KCKarlene A. Cimprich
    Karlene A. Cimprich

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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