Journal
CURRENT OPINION IN CELL BIOLOGY
Volume 21, Issue 2, Pages 237-244Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/j.ceb.2009.01.017
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Funding
- EU
- Swiss National Science Foundation
- HFSP fellowship
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During S phase, eukaryotic cells unwind and duplicate a tremendous amount of DNA, generating structures that are very sensitive to both endogenous and exogenous insults. The collision of DNA polymerases with damaged DNA or other obstructions to fork progression generates replication stress, which can evolve into fork collapse if the replisome components are not stabilized. To ensure gnome integrity, stalled replication forks are recognized by a checkpoint, whose central player is the human kinase ATR or Mec1 in S. cerevisiae. This review will discuss recent findings revealing roles of the ATIR/Mec1 kinase: both in stabilizing the replisome directly and in activating the checkpoint response to regulate origin firing, DNA repair, fork restart, and cell cycle progression.
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