SPhaseKinasen

SPhaseKinasen are a set of protein kinases that coordinate DNA replication during the S phase of the eukaryotic cell cycle. They regulate origin licensing, origin firing, and progression of replication forks, ensuring genome duplication occurs once per cycle.

In animals and yeast, the best characterized S-phase kinases are cyclin-dependent kinases (CDKs) that partner with cyclins E or A, notably CDK2. Cyclin E-CDK2 promotes the G1/S transition and initiates origin firing; Cyclin A-CDK2 continues S-phase progression and fork stability. In many systems CDK activity is tightly controlled by cyclin availability and phosphorylation status.

A second essential class is the DBF4-dependent kinase (DDK), a complex of Cdc7 kinase with its regulatory subunit Dbf4. DDK phosphorylates components of the MCM2-7 helicase complex, licensing and activating origins for replication. DDK and CDK activities cooperate to trigger origin firing and to coordinate replication progression.

In addition to initiation control, S-phase kinases interact with DNA damage and replication stress checkpoints (ATR/ATM pathways) to monitor replication and pause the cycle if problems arise. The precise composition and importance of SPhaseKinasen can vary by organism, and redundancy with other CDKs can occur; for example, CDK1 may partially substitute for CDK2 in some contexts.

Dysregulation of SPhaseKinasen is linked to genome instability and cancer. Because of this, inhibitors targeting CDKs or DDK have been explored as anti-cancer therapies, though clinical use depends on specificity and context.