Expansions of CAG Repeat Tracts are Frequent in a Yeast Mutant Defective in Okazaki Fragment Maturation
Open Access
- 1 January 1998
- journal article
- research article
- Published by Oxford University Press (OUP) in Human Molecular Genetics
- Vol. 7 (1), 69-74
- https://doi.org/10.1093/hmg/7.1.69
Abstract
To understand the causes of CAG repeat tract changes that occur in the passage of human disease alleles, we are studying the effect of replication and repair mutations on CAG repeat tracts embedded in a yeast chromosome. In this report, we examine the effect of a mutation in the RTH1/RAD27 gene encoding a deoxyribonuclease needed for removal of excess nucleotides at the 5′-end of Okazaki fragments. Deletion of the RTH1/RAD27 gene has two effects on CAG tracts. First, the rth1/rad27 mutation destabilizes CAG tracts. Second, although most tract length changes in wild-type yeast cells are tract contractions, approximately half of the changes that occur as a result of the rth1/rad27 mutation are expansions of one or more repeat units. These results support the hypothesis that tract expansions that occur during passage of human disease alleles bearing expanded CAG tracts result from excess DNA synthesis on the lagging strand of replication.Keywords
This publication has 37 references indexed in Scilit:
- Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeatsNature Genetics, 1996
- Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECTNature Genetics, 1996
- Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2Nature Genetics, 1996
- Differential pattern in tissue-specific somatic mosaicism of expanded CAG trinucleotide repeat in dentatorubral-pallidoluysian atrophy, Machado-Joseph disease, and X-linked recessive spinal and bulbar muscular atrophyJournal of the Neurological Sciences, 1996
- Gametic and somatic tissue–specific heterogeneity of the expanded SCA1 CAG repeat in spinocerebellar ataxia type 1Nature Genetics, 1995
- CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1Nature Genetics, 1994
- Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12pNature Genetics, 1994
- Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1Nature Genetics, 1993
- A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomesCell, 1993
- Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophyNature, 1991