Switch from canonical to recombination-dependent DNA synthesis by M-CDK phosphorylation of DNA Polα.

M-CDK phosphorylation of DNA Pol α triggers a switch from canonical to recombination-dependent DNA synthesis in yeast cells with under-replicated DNA.

• Why it matters: Understanding how cells balance genome stability and genetic diversity is crucial, especially since late-replicating regions evolve more rapidly, but the mechanisms remain unclear.
• What they did: Researchers investigated yeast cells with reduced origin licensing and extended S phase, showing that M-CDK phosphorylates Pol α, displacing it from forks and initiating fork collapse, which then activates error-prone recombination-based DNA synthesis.
• The result: This process enables completion of DNA replication through mechanisms similar to BIR and FoSTeS, potentially explaining the rapid evolution of late-replicating genomic regions.