The EMBO Journal · 2026
Switch from canonical to recombination-dependent DNA synthesis by M-CDK phosphorylation of DNA Polα
In yeast, this study examines what happens when a cell enters mitosis before it has finished copying its DNA. The mitotic kinase M-CDK phosphorylates DNA polymerase α: the cell then switches from canonical replication to a recombination-based DNA synthesis that is more error-prone.
- The question
- How does a cell finish copying its genome when it enters mitosis with incompletely replicated DNA, and why do late-replicating regions evolve faster?
- The approach
- Yeast with reduced licensing of replication origins and a lengthened S phase: the cells progress slowly through S phase without activating a checkpoint, and enter mitosis with under-replicated DNA.
- What the article brings
- At mitotic entry, M-CDK phosphorylates DNA polymerase α, displaces it from replication forks and makes them collapse. The DNA damage response opens a window for mitotic DNA synthesis (MiDAS), which completes replication through error-prone recombination mechanisms resembling break-induced replication (BIR) and FoSTeS.
- The limits
- The work was done in yeast; the authors present the mechanism as a potential explanation for the faster evolution of late-replicating genomic regions.
Figures from the article
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