ATR Pathway Is the Primary Pathway for Activating G sub(2)/M Checkpoint Induction After Re-replication

DNA replication is tightly controlled to ensure accurate chromosome duplication and segregation in each cell cycle. Inactivation of Geminin, an inhibitor of origin licensing, leads to re-replication in human tumor cells within the same cell cycle and triggers a G sub(2)/M checkpoint. We find that th...

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Published in:The Journal of biological chemistry 2007-10, Vol.282 (42), p.30357-30362
Main Authors: Lin, Jie Jessie, Dutta, Anindya
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Dutta, Anindya
description DNA replication is tightly controlled to ensure accurate chromosome duplication and segregation in each cell cycle. Inactivation of Geminin, an inhibitor of origin licensing, leads to re-replication in human tumor cells within the same cell cycle and triggers a G sub(2)/M checkpoint. We find that the primary pathway to signal that re-replication has been detected is the ATR kinase and the Rad9-Rad1-Hus1 (9-1-1) clamp complex together with Rad17-RFC clamp loader. ATM kinase and the Mre11-Rad50-Nbs1 complex do not appear to play significant roles in the checkpoint. Chk1 activation occurs at early stages, whereas Chk2 activation occurs much later. Overall we conclude that ATR/Chk1 pathway is activated at an early time point after the loss of Geminin and contributes to checkpoint arrest essential for the accumulation of re-replicated cells, whereas activation of the ATM/Chk2 pathway is a by-product of DNA re-replication at a later period.
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title ATR Pathway Is the Primary Pathway for Activating G sub(2)/M Checkpoint Induction After Re-replication
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