Authors
Juan de Dios Barba Tena, Riccardo Montecchi, Maxime Lambert, Thomas Defrance, Elisabeth Gueydon, Julie Petit, Marjorie Drac, Noémie Legoff, Michela Galli, Isabelle Goiffon, Thierry Gostan, Khadija El Koulali, Serge Urbach, David Toczyski, Nicolas Talarek, Etienne Schwob
Published in
The EMBO journal. Oct 10, 2026. Epub Oct 10, 2026.
Abstract
Cells preserve genome stability while occasionally generating genetic diversity through mutations and chromosomal rearrangements, but how these opposing outcomes are balanced remains unclear. Because late-replicating regions evolve more rapidly, we investigated the consequences of reduced origin licensing and lengthened S phase in yeast. Under these conditions, cells progress slowly through S phase without checkpoint activation, and enter mitosis with under-replicated DNA. We show that mitotic cyclin-dependent kinase (M-CDK) phosphorylates DNA polymerase α (Pol α), displacing it from replication forks and triggering fork collapse at mitotic entry. The resulting DNA damage response provides a window for mitotic DNA synthesis (MiDAS), enabling completion of replication through error-prone, recombination-dependent mechanisms resembling break-induced replication (BIR) and Fork Stalling & Template Switching (FoSTeS). These findings identify Pol α as a critical M-CDK target that promotes the transition from canonical replication to recombination-driven DNA synthesis when cells enter mitosis with incompletely-duplicated chromosomes. This mechanism offers a potential explanation for the accelerated evolution of late-replicating genomic regions.
PMID:
42859192
Bibliographic data and abstract were imported from PubMed on 11 Oct 2026.
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