title: Mutation at a distance caused by homopolymeric guanine repeats in Saccharomyces cerevisiae.
abstract: Mutation provides the raw material from which natural selection shapes adaptations. The rate at which new mutations arise is therefore a key factor that determines the tempo and mode of evolution. However, an accurate assessment of the mutation rate of a given organism is difficult because mutation rate varies on a fine scale within a genome. A central challenge of evolutionary genetics is to determine the underlying causes of this variation. In earlier work, we had shown that repeat sequences not only are prone to a high rate of expansion and contraction but also can cause an increase in mutation rate (on the order of kilobases) of the sequence surrounding the repeat. We perform experiments that show that simple guanine repeats 13 bp (base pairs) in length or longer (G 13+ ) increase the substitution rate 4- to 18-fold in the downstream DNA sequence, and this correlates with DNA replication timing (R = 0.89). We show that G 13+ mutagenicity results from the interplay of both error-prone translesion synthesis and homologous recombination repair pathways. The mutagenic repeats that we study have the potential to be exploited for the artificial elevation of mutation rate in systems biology and synthetic biology applications.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McDonald
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Yen-Hsin
authors.initials: YH
authors.lastname: Yu
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Jheng-Fen
authors.initials: JF
authors.lastname: Guo
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan.; Graduate Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Shin Yen
authors.initials: SY
authors.lastname: Chong
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Cheng-Fu
authors.identifier: 0000-0002-8875-8152
authors.initials: CF
authors.lastname: Kao
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Jun-Yi
authors.initials: JY
authors.lastname: Leu
mesh_terms: D042622:DNA Repeat Expansion; D004261:DNA Replication; D006147:Guanine / Q000737:chemistry*; D008954:Models, Biological; D016296:Mutagenesis; D009154:Mutation; D059645:Mutation Rate; D051721:Rad52 DNA Repair and Recombination Protein / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D020080:Tandem Repeat Sequences; D014158:Transcription, Genetic
chemical_list: D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; D006147:Guanine
keywords: Mutation at a distance; evolution; homologous recombination; mutator; repeat sequence; translesion synthesis