Evidence for preferential mismatch repair of lagging strand DNA replication errors in yeast

Youri I Pavlov, Ibrahim M. Mian, Thomas A. Kunkel

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Duplex DNA is replicated in the 5′-3′ direction by coordinated copying of leading and lagging strand templates with somewhat different proteins and mechanics, providing the potential for differences in the fidelity of replication of the two strands. We previously showed that in Saccharomyces cerevisiae, active replication origins establish a strand bias in the rate of base substitutions resulting from replication of unrepaired 8-oxo-guanine (GO) in DNA [1]. Lower mutagenesis was associated with replicating lagging strand templates. Here, we test the hypothesis that this bias is due to more efficient repair of lagging stand mismatches by measuring mutation rates in ogg1 strains with a reporter allele in two orientations at loci on opposite sides of a replication origin on chromosome III. We compare a MMR-proficient strain to strains deleted for the MMR genes MSH2, MSH6, MLH1, or EXOI. Loss of MMR reduces the strand bias by preferentially increasing mutagenesis for lagging strand replication. We conclude that GO-A mismatches generated during lagging strand replication are more efficiently repaired. This is consistent with the hypothesis that 5′ ends of Okazaki fragments and PCNA, present at high density during lagging strand replication, are used as strand discrimination signals for mismatch repair in vivo.

Original languageEnglish (US)
Pages (from-to)744-748
Number of pages5
JournalCurrent Biology
Volume13
Issue number9
DOIs
StatePublished - Apr 29 2003

Fingerprint

Replication Origin
DNA Mismatch Repair
DNA replication
DNA Replication
Mutagenesis
Yeast
replication origin
Repair
Yeasts
yeasts
mutagenesis
DNA
Proliferating Cell Nuclear Antigen
Guanine
Mutation Rate
Mechanics
Saccharomyces cerevisiae
Copying
Chromosomes
guanine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Evidence for preferential mismatch repair of lagging strand DNA replication errors in yeast. / Pavlov, Youri I; Mian, Ibrahim M.; Kunkel, Thomas A.

In: Current Biology, Vol. 13, No. 9, 29.04.2003, p. 744-748.

Research output: Contribution to journalArticle

Pavlov, Youri I ; Mian, Ibrahim M. ; Kunkel, Thomas A. / Evidence for preferential mismatch repair of lagging strand DNA replication errors in yeast. In: Current Biology. 2003 ; Vol. 13, No. 9. pp. 744-748.
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