Cds1

Cds1 is a protein kinase in the fission yeast Schizosaccharomyces pombe that acts as a central effector of the S-phase checkpoint in the DNA damage response. It is functionally analogous to CHK2 in vertebrates and operates downstream of the ATR-like Rad3 kinase. Cds1 is activated in response to replication stress and DNA damage, such as fork stalling induced by hydroxyurea, through Rad3-dependent phosphorylation facilitated by mediator proteins such as Mrc1. Upon activation, Cds1 signals to halt cell cycle progression and help stabilize replication forks.

Downstream effects of Cds1 activation include inhibition of mitotic entry via sustained inhibitory phosphorylation of the Cdc25 phosphatase, thereby keeping the Cdc2–cyclin B complex inactive. Cds1 also contributes to the stabilization and protection of stalled forks and can influence origin firing during replication stress to preserve genome integrity. The overall checkpoint function reduces the risk of chromosome breakage and genetic information loss under genotoxic conditions.

Cds1 is a serine/threonine kinase with a conserved catalytic kinase domain and is largely nonessential for normal growth but becomes important for survival under DNA-damaging conditions. Mutants show sensitivity to replication inhibitors and DNA-damaging agents and display defects in S-phase progression when stressed. In humans, CHK2 is considered an analogous role, though Cds1 and CHK2 are not direct orthologs.

Disambiguation: the acronym CDS1 can refer to other genes in different organisms or to the human CDS1 gene encoding cytidine triphosphate synthase 1 in certain contexts; this article focuses on Cds1 in Schizosaccharomyces pombe.