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Published online
doi:10.1083/jcb.200811083
The Journal of Cell Biology, Vol. 185, No. 3, 423-437
The Rockefeller University Press, 0021-9525 $30.00
© Enserink et al.
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Article

Cdc28/Cdk1 positively and negatively affects genome stability in S. cerevisiae



Jorrit M. Enserink1,2,3,4, Hans Hombauer1,2,3,4, Meng-Er Huang5, and Richard D. Kolodner1,2,3,4

1 Ludwig Institute for Cancer Research, 2 Department of Medicine, 3 Department of Cellular and Molecular Medicine, and 4 Cancer Center, University of California, San Diego School of Medicine, La Jolla, CA 92093
5 Centre National de la Recherche Scientifique Unité Mixte de Recherche 2027, Institut Curie, Centre Universitaire, 91405 Orsay, France

Correspondence to Richard D. Kolodner: rkolodner{at}ucsd.edu

We studied the function of the cyclin-dependent kinase Cdc28 (Cdk1) in the DNA damage response and maintenance of genome stability using Saccharomyces cerevisiae. Reduced Cdc28 activity sensitizes cells to chronic DNA damage, but Cdc28 is not required for cell viability upon acute exposure to DNA-damaging agents. Cdc28 is also not required for activation of the DNA damage and replication checkpoints. Chemical–genetic analysis reveals that CDC28 functions in an extensive network of pathways involved in maintenance of genome stability, including homologous recombination, sister chromatid cohesion, the spindle checkpoint, postreplication repair, and telomere maintenance. In addition, Cdc28 and Mre11 appear to cooperate to prevent mitotic catastrophe after DNA replication arrest. We show that reduced Cdc28 activity results in suppression of gross chromosomal rearrangements (GCRs), indicating that Cdc28 is required for formation or recovery of GCRs. Thus, we conclude that Cdc28 functions in a genetic network that supports cell viability during DNA damage while promoting the formation of GCRs.

J.M. Enserink's present address is Dept. of Molecular Biology, Rikshospitalet University Hospital, NO-0027 Oslo, Norway.

Abbreviations used in this paper: CKI, Cdk inhibitor; CPT, camptothecin; DSB, DNA double-strand break; GCR, gross chromosomal rearrangement; HR, homologous recombination; HU, hydroxyurea; MMS, methylmethanesulfonate; NHEJ, nonhomologous end joining; PFGE, pulsed-field gel electrophoresis; RPA, replication protein A; ssDNA, single-stranded DNA; WT, wild type; YPD, yeast extract/peptone/dextrose.

© 2009 Enserink et al.
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