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Impairment of the non-catalytic subunit Dpb2 of DNA Pol ɛ results in increased involvement of Pol δ on the leading strand
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, Warsaw, Poland.
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, Warsaw, Poland.
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.ORCID iD: 0000-0003-2713-5813
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.ORCID iD: 0000-0003-1708-8259
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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, YTAK002Available from: 2023-08-01 Created: 2023-08-01 Last updated: 2025-04-24Bibliographically approved

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Sharma, SushmaChabes, Andrei

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