A Major Role of DNA Polymerase δ in Replication of Both the Leading and Lagging DNA Strands

Robert E. Johnson, Roland Klassen, Louise Prakash, Satya Prakash

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Genetic studies with S.cerevisiae Polδ (pol3-L612M) and Polε (pol2-M644G) mutant alleles, each of which display a higher rate for the generation of a specific mismatch, have led to the conclusion that Polε is the primary leading strand replicase and that Polδ is restricted to replicating the lagging strand template. Contrary to this widely accepted view, here we show that Polδ plays a major role in the replication of both DNA strands, and that the paucity of pol3-L612M-generated errors on the leading strand results from their more proficient removal. Thus, the apparent lack of Polδ contribution to leading strand replication is due to differential mismatch removal rather than differential mismatch generation. Altogether, our genetic studies with Pol3 and Pol2 mutator alleles support the conclusion that Polδ, and not Polε, is the major DNA polymerase for carrying out both leading and lagging DNA synthesis.

Original languageEnglish (US)
Pages (from-to)163-175
Number of pages13
JournalMolecular Cell
Volume59
Issue number2
DOIs
StatePublished - Jul 16 2015

Fingerprint

DNA-Directed DNA Polymerase
Alleles
DNA
DNA Replication
Saccharomyces cerevisiae

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

A Major Role of DNA Polymerase δ in Replication of Both the Leading and Lagging DNA Strands. / Johnson, Robert E.; Klassen, Roland; Prakash, Louise; Prakash, Satya.

In: Molecular Cell, Vol. 59, No. 2, 16.07.2015, p. 163-175.

Research output: Contribution to journalArticle

@article{a5e39e94f91841d9807f7d24e4b1f6f6,
title = "A Major Role of DNA Polymerase δ in Replication of Both the Leading and Lagging DNA Strands",
abstract = "Genetic studies with S.cerevisiae Polδ (pol3-L612M) and Polε (pol2-M644G) mutant alleles, each of which display a higher rate for the generation of a specific mismatch, have led to the conclusion that Polε is the primary leading strand replicase and that Polδ is restricted to replicating the lagging strand template. Contrary to this widely accepted view, here we show that Polδ plays a major role in the replication of both DNA strands, and that the paucity of pol3-L612M-generated errors on the leading strand results from their more proficient removal. Thus, the apparent lack of Polδ contribution to leading strand replication is due to differential mismatch removal rather than differential mismatch generation. Altogether, our genetic studies with Pol3 and Pol2 mutator alleles support the conclusion that Polδ, and not Polε, is the major DNA polymerase for carrying out both leading and lagging DNA synthesis.",
author = "Johnson, {Robert E.} and Roland Klassen and Louise Prakash and Satya Prakash",
year = "2015",
month = "7",
day = "16",
doi = "10.1016/j.molcel.2015.05.038",
language = "English (US)",
volume = "59",
pages = "163--175",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - A Major Role of DNA Polymerase δ in Replication of Both the Leading and Lagging DNA Strands

AU - Johnson, Robert E.

AU - Klassen, Roland

AU - Prakash, Louise

AU - Prakash, Satya

PY - 2015/7/16

Y1 - 2015/7/16

N2 - Genetic studies with S.cerevisiae Polδ (pol3-L612M) and Polε (pol2-M644G) mutant alleles, each of which display a higher rate for the generation of a specific mismatch, have led to the conclusion that Polε is the primary leading strand replicase and that Polδ is restricted to replicating the lagging strand template. Contrary to this widely accepted view, here we show that Polδ plays a major role in the replication of both DNA strands, and that the paucity of pol3-L612M-generated errors on the leading strand results from their more proficient removal. Thus, the apparent lack of Polδ contribution to leading strand replication is due to differential mismatch removal rather than differential mismatch generation. Altogether, our genetic studies with Pol3 and Pol2 mutator alleles support the conclusion that Polδ, and not Polε, is the major DNA polymerase for carrying out both leading and lagging DNA synthesis.

AB - Genetic studies with S.cerevisiae Polδ (pol3-L612M) and Polε (pol2-M644G) mutant alleles, each of which display a higher rate for the generation of a specific mismatch, have led to the conclusion that Polε is the primary leading strand replicase and that Polδ is restricted to replicating the lagging strand template. Contrary to this widely accepted view, here we show that Polδ plays a major role in the replication of both DNA strands, and that the paucity of pol3-L612M-generated errors on the leading strand results from their more proficient removal. Thus, the apparent lack of Polδ contribution to leading strand replication is due to differential mismatch removal rather than differential mismatch generation. Altogether, our genetic studies with Pol3 and Pol2 mutator alleles support the conclusion that Polδ, and not Polε, is the major DNA polymerase for carrying out both leading and lagging DNA synthesis.

UR - http://www.scopus.com/inward/record.url?scp=84937413584&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84937413584&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2015.05.038

DO - 10.1016/j.molcel.2015.05.038

M3 - Article

C2 - 26145172

AN - SCOPUS:84937413584

VL - 59

SP - 163

EP - 175

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 2

ER -