Journal
DNA REPAIR
Volume 129, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.dnarep.2023.103541
Keywords
DNA polymerase epsilon; Pol e; Dpb2; DNA polymerase delta; Pol 6; CMG (Cdc45 Mcm2-7 GINS); Replication fork; DNA replication fidelity; Genome stability
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The generally accepted model proposes that Pol e is responsible for leading strand synthesis, while Pol 6 catalyzes lagging strand synthesis. Pol e has been found to interact with the CMG helicase [Cdc45 Mcm2-7 GINS(Psf1-3, Sld5)] to target the leading strand. The proper functioning of the CMG-Pol e complex is crucial for DNA replication progression and accuracy. Dpb2p, a non-catalytic subunit of Pol e, plays a critical role in maintaining the correct architecture of the replisome by connecting Pol e and the CMG complex. Using a temperature-sensitive dpb2-100 mutant and a genetic system that identifies the involvement of Pol 6 in replicating specific DNA strands, this study demonstrates an increased contribution of Pol 6 to leading strand replication in yeast cells with impaired Dpb2 subunit.
The generally accepted model assumes that leading strand synthesis is performed by Pol e, while lagging-strand synthesis is catalyzed by Pol 6. Pol e has been shown to target the leading strand by interacting with the CMG helicase [Cdc45 Mcm2-7 GINS(Psf1-3, Sld5)]. Proper functioning of the CMG-Pol e, the helicase-polymerase complex is essential for its progression and the fidelity of DNA replication. Dpb2p, the essential non-catalytic subunit of Pol e plays a key role in maintaining the correct architecture of the replisome by acting as a link between Pol e and the CMG complex. Using a temperature-sensitive dpb2-100 mutant previously isolated in our laboratory, and a genetic system which takes advantage of a distinct mutational signature of the Pol 6-L612M variant which allows detection of the involvement of Pol 6 in the replication of particular DNA strands we show that in yeast cells with an impaired Dpb2 subunit, the contribution of Pol 6 to the replication of the leading strand is significantly increased.
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