title: Genomic deletions and point mutations induced in Saccharomyces cerevisiae by the trinucleotide repeats (GAA·TTC) associated with Friedreich's ataxia.
abstract: Expansion of certain trinucleotide repeats causes several types of human diseases, and such tracts are associated with the formation of deletions and other types of genetic rearrangements in Escherichia coli, yeast, and mammalian cells. Below, we show that long (230 repeats) tracts of the trinucleotide associated with Friedreich's ataxia (GAA·TTC) stimulate both large (>50 bp) deletions and point mutations in a reporter gene located more than 1 kb from the repetitive tract. Sequence analysis of deletion breakpoints indicates that the deletions reflect non-homologous end joining of double-stranded DNA breaks (DSBs) initiated in the tract. The tract-induced point mutations appear to reflect a different mechanism involving single-strand annealing of DNA molecules generated by DSBs within the tract, followed by filling-in of single-stranded gaps by the error-prone DNA polymerase zeta.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Margaret
authors.initials: M
authors.lastname: Dominska
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Gawel
authors.forename: Patricia W
authors.initials: PW
authors.lastname: Greenwell
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Petes
mesh_terms: D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D004277:DNA, Single-Stranded / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D005621:Friedreich Ataxia / Q000235:genetics*; D017353:Gene Deletion; D017930:Genes, Reporter / Q000235:genetics; D016681:Genome, Fungal / Q000235:genetics; D006801:Humans; D017354:Point Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D018911:Trinucleotide Repeats
chemical_list: D004277:DNA, Single-Stranded; D029701:Saccharomyces cerevisiae Proteins; C425929:DNA polymerase zeta; D004259:DNA-Directed DNA Polymerase