Replication checkpoint kinase Cds1 regulates recombinational repair protein Rad60.
Genome integrity is protected by Cds1 (Chk2), a checkpoint kinase that stabilizes arrested replication forks. How Cds1 accomplishes this task is unknown. We report that Cds1 interacts with Rad60, a protein required for recombinational repair in fission yeast. Cds1 activation triggers Rad60 phosphorylation and nuclear delocalization. A Rad60 mutant that inhibits regulation by Cds1 renders cells specifically sensitive to replication fork arrest. Genetic and biochemical studies indicate that Rad60 functions codependently with Smc5 and Smc6, subunits of an SMC (structural maintenance of chromosomes) complex required for recombinational repair. These studies indicate that regulation of Rad60 is an important part of the replication checkpoint response controlled by Cds1. We propose that control of Rad60 regulates recombination events at stalled forks.
Boddy
Michael N
MN
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Shanahan
Paul
P
McDonald
W Hayes
WH
Lopez-Girona
Antonia
A
Noguchi
Eishi
E
Yates III
John R
JR
Russell
Paul
P
D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D064447:Checkpoint Kinase 2; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D015151:Immunoblotting; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011995:Recombination, Genetic; D004718:Saccharomycetales; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; C455501:Rad60 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C578636:Cds1 protein, S pombe; D017346:Protein Serine-Threonine Kinases