A conserved phosphorylation mechanism for regulating the interaction between the CMG replicative helicase and its forked DNA substrate.

ABSTRACT: The CMG helicase is a crucial enzyme complex that plays a vital role in the replication of genomic DNA in eukaryotes. Besides unwinding the DNA template and coordinating the replisome's structure, it is also a key target for signaling pathways that regulate the replication process. We show that a specific serine/threonine residue in the MCM3 subunit of CMG, which has been previously linked to phosphorylation-dependent control mechanisms of genomic DNA replication in human cells, is a conserved phosphorylation site for Chk1 and potentially other protein kinases. This suggests a conserved regulatory mechanism associated with it in metazoans and several other eukaryotes, including budding yeast. Our in vitro analysis links this mechanism directly to the modulation of the CMG helicase activity

SUBMITTER: Koit S 

PROVIDER: S-EPMC12018195 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature