Published in

Rockefeller University Press, Journal of Cell Biology, 6(204), p. 1075-1075, 2014

DOI: 10.1083/jcb.20131008303042014c

Rockefeller University Press, Journal of Cell Biology, 4(204), p. 507-522, 2014

DOI: 10.1083/jcb.201310083

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CDK phosphorylation of SLD-2 is required for replication initiation and germline development in C. elegans

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Cyclin-dependent kinase (CDK) plays a vital role in proliferation control across eukaryotes. Despite this, how CDK mediates cell cycle and developmental transitions in metazoa is poorly understood. In this paper, we identify orthologues of Sld2, a CDK target that is important for DNA replication in yeast, and characterize SLD-2 in the nematode worm Caenorhabditis elegans. We demonstrate that SLD-2 is required for replication initiation and the nuclear retention of a critical component of the replicative helicase CDC-45 in embryos. SLD-2 is a CDK target in vivo, and phosphorylation regulates the interaction with another replication factor, MUS-101. By mutation of the CDK sites in sld-2, we show that CDK phosphorylation of SLD-2 is essential in C. elegans. Finally, using a phosphomimicking sld-2 mutant, we demonstrate that timely CDK phosphorylation of SLD-2 is an important control mechanism to allow normal proliferation in the germline. These results determine an essential function of CDK in metazoa and identify a developmental role for regulated SLD-2 phosphorylation.