Cdc28/Cdk1 positively and negatively affects genome stability in S. cerevisiae.
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.
Enserink
Jorrit M
JM
Department of Medicine, Cancer Center, Ludwig Institute for Cancer Research, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA.
Hombauer
Hans
H
Huang
Meng-Er
ME
Kolodner
Richard D
RD
D016203:CDC2 Protein Kinase / Q000235:genetics*; D017489:CDC28 Protein Kinase, S cerevisiae / Q000235:genetics* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000235:genetics; D004261:DNA Replication / Q000187:drug effects / Q000235:genetics; D042822:Genomic Instability; D008938:Mitosis / Q000235:genetics; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010692:Phleomycins / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000528:radiation effects; D014466:Ultraviolet Rays
D019384:Nucleic Acid Synthesis Inhibitors; D010692:Phleomycins; D016203:CDC2 Protein Kinase; D017489:CDC28 Protein Kinase, S cerevisiae