By phosphorylating specific replication factors, cell cycle kinases ensure that eukaryotic DNA replication is initiated once and only once per mitotic cell division. New work in The EMBO Journal now reveals how DDK‐mediated phosphorylation of Mcm2‐7 helicase subunits is read out by Sld3, which provides further integration with CDK phosphorylation.
See also: TD Deegan et al
Eukaryotic DNA replication is strictly coupled to cell cycle regulation, with the initiation step sensing and integrating signals from the cell cycle machinery. Replication initiates from so‐called origin sequences on chromosomal DNA, which in budding yeast are bound by origin recognition complex (ORC) proteins throughout the cell cycle. In the G1 phase, hexameric Mcm2‐7 helicase core complexes, which on their own do not yet display helicase activity, load onto ORC‐bound origins to form pre‐replicative complexes (pre‐RCs). After activation of the master cell cycle protein kinase CDK (cyclin‐dependent kinase) in late G1, budding yeast CDK phosphorylates two key replication factors, Sld2 and Sld3. This phosphorylation enhances interactions between Sld2, Sld3 and Dpb11, which in turn promotes the formation of active replicative DNA helicase, Cdc45‐Mcm2‐7‐GINS (CMG), on replication origins. A second protein kinase, Dbf4‐dependent kinase (DDK), is also activated at …
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