Checkpoint Adaptation and Recovery: Back with Polo after the Break

S. cerevisiae cells that are unable to repair a double strand break ultimatelyescape the DNA damage checkpoint arrest and enter mitosis. This process called'adaptation' depends on functional Cdc5, a Polo-like kinase, and was long thoughtto be limited to single-cell organisms. However, the recent finding that Xenopusextracts can adapt to a long-lasting stall in DNA replication indicates thatcheckpoint adaptation does also occur in multicellular organisms. Interestingly, theXenopus Polo-like kinase (Plx1) plays an important role in this adaptation. To addto this, data from our laboratory have shown that the human Polo-like kinase (Plk1)is also required for cell cycle re-entry following a DNA damage-induced arrest. Buthere, Plk1 was shown to be required for bona-fide checkpoint recovery, rather thanadaptation. That is, Plk1 is required to restart the cell cycle once all of the damage isrepaired and checkpoint signaling is turned off. While the target of Plx1 duringadaptation is a component of the checkpoint machinery (Claspin), the target of Plk1during recovery turns out to be a mitotic regulator (Wee1). Here, we discuss some ofthe remarkable similarities and subtle differences in the molecular mechanisms thatcontrol checkpoint adaptation and recovery, and the role of Polo-like kinasestherein.

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