Lee C, et al. (2010) Alternative mechanisms for coordinating polymerase alpha and MCM helicase. Mol Cell Biol 30(2):423-35
Abstract: Functional coordination between DNA replication helicases and DNA polymerases at replication forks, achieved through physical linkages, has been demonstrated in prokaryotes but not in eukaryotes. In S. cerevisiae, we showed that mutations that compromise the activity of the MCM helicase enhance the physical stability of DNA polymerase alpha in the absence of their presumed linker, Mcm10. Mcm10 is an essential DNA replication protein implicated in the stable assembly of the replisome by virtue of its interaction with MCM2-7 helicase and Polalpha. Dominant mcm2 suppressors of mcm10 mutants restore viability by restoring the stability of Polalpha, without restoring the stability of Mcm10, in a Mec1 dependent manner. In this process, the ssDNA accumulation observed in the mcm10 mutant is suppressed. The activities of key checkpoint regulators known to be important for replication fork stabilization contribute to the efficiency of suppression. These results suggest that Mcm10 plays two important roles as a linker of the MCM helicase and Pol alpha at the elongating replication fork; first to coordinate the activities of these two molecular motors, and second to ensure their physical stability and the integrity of the replication fork.
|Status: Published||Type: Journal Article||PubMed ID: 19917723|
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