Impairment of the non-catalytic subunit Dpb2 of DNA Pol ɛ results in increased involvement of Pol δ on the leading strandShow others and affiliations
2023 (English)In: DNA Repair, ISSN 1568-7864, E-ISSN 1568-7856, Vol. 129, article id 103541Article in journal (Refereed) Published
Abstract [en]
The generally accepted model assumes that leading strand synthesis is performed by Pol ε, while lagging-strand synthesis is catalyzed by Pol δ. Pol ε 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 ɛ, the helicase-polymerase complex is essential for its progression and the fidelity of DNA replication. Dpb2p, the essential non-catalytic subunit of Pol ε plays a key role in maintaining the correct architecture of the replisome by acting as a link between Pol ε 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 δ-L612M variant which allows detection of the involvement of Pol δ in the replication of particular DNA strands we show that in yeast cells with an impaired Dpb2 subunit, the contribution of Pol δ to the replication of the leading strand is significantly increased.
Place, publisher, year, edition, pages
Elsevier, 2023. Vol. 129, article id 103541
Keywords [en]
CMG (Cdc45 Mcm2–7 GINS), DNA polymerase delta, DNA polymerase epsilon, DNA replication fidelity, Dpb2, Genome stability, Pol δ, Pol ε, Replication fork
National Category
Medical Genetics and Genomics
Identifiers
URN: urn:nbn:se:umu:diva-212493DOI: 10.1016/j.dnarep.2023.103541ISI: 001048000100001PubMedID: 37481989Scopus ID: 2-s2.0-85165586443OAI: oai:DiVA.org:umu-212493DiVA, id: diva2:1785207
Funder
Swedish Cancer SocietySwedish Research Council, SNM79Swedish Research Council, YTAK0022023-08-012023-08-012025-04-24Bibliographically approved