Abstract
Expansion of DNA trinucleotide repeats (TNRs) is the causative mutation in a growing number of human genetic diseases. Large expansions of a CTG tract were obtained and shown by genetic and physical assays to be length-dependent sites of chromosome breakage in Saccharomyces cerevisiae. Deletion of RAD27, which encodes a nuclease involved in Okazaki fragment processing, caused length-dependent destabilization of CTG tracts and a substantial increase in expansion frequency. The genetic assay described here can be used to evaluate other factors that induce TNR expansion or chromosome fragility in humans.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Chromosome Breakage*
-
Chromosome Fragility*
-
Chromosomes, Fungal / metabolism*
-
DNA Damage
-
DNA Repair
-
DNA Replication
-
DNA, Fungal / metabolism
-
Electrophoresis, Gel, Pulsed-Field
-
Exodeoxyribonuclease V
-
Exodeoxyribonucleases / genetics
-
Gene Deletion
-
Genes, Fungal
-
Humans
-
Hydroxyurea / pharmacology
-
Recombination, Genetic
-
Saccharomyces cerevisiae / genetics*
-
Saccharomyces cerevisiae / metabolism
-
Transformation, Genetic
-
Trinucleotide Repeat Expansion*
-
Trinucleotide Repeats / genetics*
Substances
-
DNA, Fungal
-
Exodeoxyribonucleases
-
Exodeoxyribonuclease V
-
Hydroxyurea