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PMID: 10924464 Published · ppublish English Journal Article

The impact of lagging strand replication mutations on the stability of CAG repeat tracts in yeast.

Genetics ·Vol. 155 ·No. 4 ·2000-08-00 ·Pages 1657-65

Ireland MJ, Reinke SS, Livingston DM

Abstract

We have examined the stability of long tracts of CAG repeats in yeast mutants defective in enzymes suspected to be involved in lagging strand replication. Alleles of DNA ligase (cdc9-1 and cdc9-2) destabilize CAG tracts in the stable tract orientation, i.e., when CAG serves as the lagging strand template. In this orientation nearly two-thirds of the events recorded in the cdc9-1 mutant were tract expansions. While neither DNA ligase allele significantly increases the frequency of tract-length changes in the unstable orientation, the cdc9-1 mutant produced a significant number of expansions in tracts of this orientation. A mutation in primase (pri2-1) destabilizes tracts in both the stable and the unstable orientations. Mutations in a DNA helicase/deoxyribonuclease (dna2-1) or in two RNase H activities (rnh1Delta and rnh35Delta) do not have a significant effect on CAG repeat tract stability. We interpret our results in terms of the steps of replication that are likely to lead to expansion and to contraction of CAG repeat tracts.

MeSH Terms
Alleles DNA Helicases/genetics DNA Ligases/genetics DNA Primase/genetics DNA Replication/genetics Genes, Fungal Models, Genetic Mutation Phenotype Ribonuclease H/genetics Trinucleotide Repeat Expansion Trinucleotide Repeats
Chemicals
DNA Primase Ribonuclease H DNA Helicases DNA Ligases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ireland M J
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Reinke S S
Livingston D M
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Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
0016-6731
DOI
10.1093/genetics/155.4.1657
Published
2000-08-00
Pages
1657-65
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC1461208
Subset
IM
External Links
PubMed source DOI: 10.1093/genetics/155.4.1657 PMC Full Text View journal details
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