Mcm2-7 Is an Active Player in the DNA Replication Checkpoint Signaling Cascade via Proposed Modulation of Its DNA Gate.

The DNA replication checkpoint (DRC) monitors and responds to stalled replication forks to prevent genomic instability. How core replication factors integrate into this phosphorylation cascade is incompletely understood. Here, through analysis of a unique mcm allele targeting a specific ATPase active site (mcm2DENQ), we show that the Mcm2-7 replicative helicase ...
has a novel DRC function as part of the signal transduction cascade. This allele exhibits normal downstream mediator (Mrc1) phosphorylation, implying DRC sensor kinase activation. However, the mutant also exhibits defective effector kinase (Rad53) activation and classic DRC phenotypes. Our previous in vitro analysis showed that the mcm2DENQ mutation prevents a specific conformational change in the Mcm2-7 hexamer. We infer that this conformational change is required for its DRC role and propose that it allosterically facilitates Rad53 activation to ensure a replication-specific checkpoint response.
Mesh Terms:
Catalytic Domain, Cell Cycle Proteins, Checkpoint Kinase 2, DNA Replication, DNA, Fungal, DNA-Binding Proteins, Minichromosome Maintenance Proteins, Mutation, Nuclear Proteins, Protein Multimerization, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction
Mol. Cell. Biol.
Date: Jun. 01, 2015
Download Curated Data For This Publication
206049
Switch View:
  • Interactions 20