Evidence that DNA polymerase δ contributes to initiating leading strand DNA replication in Saccharomyces cerevisiae

Nature Communications
Marta A GarbaczThomas A Kunkel

Abstract

To investigate nuclear DNA replication enzymology in vivo, we have studied Saccharomyces cerevisiae strains containing a pol2-16 mutation that inactivates the catalytic activities of DNA polymerase ε (Pol ε). Although pol2-16 mutants survive, they present very tiny spore colonies, increased doubling time, larger than normal cells, aberrant nuclei, and rapid acquisition of suppressor mutations. These phenotypes reveal a severe growth defect that is distinct from that of strains that lack only Pol ε proofreading (pol2-4), consistent with the idea that Pol ε is the major leading-strand polymerase used for unstressed DNA replication. Ribonucleotides are incorporated into the pol2-16 genome in patterns consistent with leading-strand replication by Pol δ when Pol ε is absent. More importantly, ribonucleotide distributions at replication origins suggest that in strains encoding all three replicases, Pol δ contributes to initiation of leading-strand replication. We describe two possible models.

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Citations

Jan 2, 2019·Proceedings of the National Academy of Sciences of the United States of America·Ryan MayleMichael E O'Donnell
Feb 26, 2020·Genes·Julius Muellner, Kristina H Schmidt
Sep 8, 2019·Current Genetics·Marta A GarbaczThomas A Kunkel
Feb 16, 2020·The Journal of Biological Chemistry·Alexandra N Khristich, Sergei M Mirkin
Sep 7, 2019·Nature Communications·Zhi-Xiong ZhouThomas A Kunkel
Sep 5, 2020·Critical Reviews in Biochemistry and Molecular Biology·Thomas A Guilliam, Joseph T P Yeeles
Dec 28, 2018·Genes·Wendy LeungAnja-Katrin Bielinsky
Apr 29, 2020·Nature Structural & Molecular Biology·Sujan Devbhandari, Dirk Remus
Aug 10, 2019·Biochemical Society Transactions·Nitin Kapadia, Rodrigo Reyes-Lamothe
Mar 4, 2020·Proceedings of the National Academy of Sciences of the United States of America·Chelsea R BulockPolina V Shcherbakova
Oct 2, 2019·International Journal of Molecular Sciences·Jose-Antonio Pedroza-GarciaCécile Raynaud
Apr 29, 2020·Nature Structural & Molecular Biology·Thomas A Guilliam, Joseph T P Yeeles
Sep 10, 2019·Molecular Cell·Roberto A DonnianniLorraine S Symington
Jan 20, 2021·Critical Reviews in Biochemistry and Molecular Biology·Zhi-Xiong ZhouThomas A Kunkel
Dec 17, 2020·International Journal of Molecular Sciences·Milena Denkiewicz-KrukIwona J Fijalkowska
Dec 20, 2020·Experimental & Molecular Medicine·Kyoo-Young Lee, Su Hyung Park
Jan 29, 2021·The Journal of Biological Chemistry·Alexandra N Khristich, Sergei M Mirkin
Oct 13, 2020·Trends in Genetics : TIG·Roberto Bellelli, Simon J Boulton
May 12, 2021·Wellcome Open Research·Róbert Zach, Antony M Carr
Apr 11, 2021·Proceedings of the National Academy of Sciences of the United States of America·Nichole OwenAmanda K McCullough
May 15, 2021·Nature Communications·Mengshi WuRosa Lozano-Durán
Aug 14, 2021·Trends in Cell Biology·Esther A Epum, James E Haber

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Datasets Mentioned

BETA
GSE101698

Methods Mentioned

BETA
PCR
dissections
flow cytometry
HydEn-seq

Software Mentioned

BedGraph
cutadapt
GINS
DESeq
CLCGenomics Workbench
eSPAN
FlowJo
bowtie
FACSDiva
HydEn

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