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

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  • Philip Zegerman

    (Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Present address: Wellcome Trust/Cancer Research UK Gurdon Institute, Department of Zoology, University of Cambridge, Cambridge CB2 1QN, UK.)

  • John F. X. Diffley

    (Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK)

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.

Suggested Citation

  • Philip Zegerman & John F. X. Diffley, 2010. "Checkpoint-dependent inhibition of DNA replication initiation by Sld3 and Dbf4 phosphorylation," Nature, Nature, vol. 467(7314), pages 474-478, September.
    • Handle: RePEc:nat:nature:v:467:y:2010:i:7314:d:10.1038_nature09373
    DOI: 10.1038/nature09373
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