Checkpoint-dependent inhibition of DNA replication initiation by Sld3 and Dbf4 phosphorylation

Philip Zegerman and John F. X. Diffley ()
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Philip Zegerman: Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
John F. X. Diffley: Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK

Nature, 2010, vol. 467, issue 7314, 474-478

Abstract: Stop at the intra-S checkpoint Two classes of kinases, CDK and DDK, facilitate the initiation of DNA replication in S phase. In two studies, the Diffley and Toczyski labs show that when damage is sensed, another kinase — the checkpoint kinase Rad53 — halts replication by inhibiting both the CDK and DDK pathways through the phosphorylation of Sld3 and Dbf4, respectively. These results reveal that regulation of the firing of origins is the means by which the intra-S checkpoint slows S phase.

Date: 2010
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DOI: 10.1038/nature09373

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