Chromosomal rearrangements occur in S. cerevisiae rfa1 mutator mutants due to mutagenic lesions processed by double-strand-break repair

Mol Cell. 1998 Jul;2(1):9-22. doi: 10.1016/s1097-2765(00)80109-4.

Abstract

Three temperature-sensitive S. cerevisiae RFA1 alleles were found to cause elevated mutation rates. These mutator phenotypes resulted from the accumulation of base substitutions, frameshifts, gross deletions (8 bp-18 kb), and nonreciprocal translocations. A representative rfa1 mutation exhibited a growth defect in conjunction with rad51, rad52, or rad10 mutations, suggesting an accumulation of double-strand breaks. rad10 and rad52 mutations eliminated deletion and translocation formation, whereas a rad51 mutation increased the frequency of these events and revealed a new class of genetic rearrangements--loss of a portion of a chromosome arm combined with telomere addition. The breakpoints of the translocations and deletions were flanked by imperfect direct repeats of 2-20 bp, similar to the breakpoint structures observed at translocations and gross deletions, including LOH events, underlying human cancer and other hereditary diseases.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Base Sequence
  • Chromosome Aberrations*
  • Chromosome Deletion
  • Chromosomes, Fungal / ultrastructure*
  • DNA / genetics*
  • DNA Damage
  • DNA Repair*
  • DNA Replication
  • DNA, Fungal / genetics*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Endonucleases / genetics
  • Frameshift Mutation
  • Fungal Proteins / genetics
  • Humans
  • Loss of Heterozygosity
  • Models, Genetic
  • Molecular Sequence Data
  • Mutagenesis
  • Rad51 Recombinase
  • Rad52 DNA Repair and Recombination Protein
  • Repetitive Sequences, Nucleic Acid
  • Replication Protein A
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins*
  • Single-Strand Specific DNA and RNA Endonucleases
  • Species Specificity
  • Translocation, Genetic

Substances

  • DNA, Fungal
  • DNA-Binding Proteins
  • Fungal Proteins
  • RAD52 protein, S cerevisiae
  • RPA1 protein, human
  • Rad52 DNA Repair and Recombination Protein
  • Replication Protein A
  • Saccharomyces cerevisiae Proteins
  • DNA
  • RAD51 protein, S cerevisiae
  • RAD51 protein, human
  • Rad51 Recombinase
  • Endonucleases
  • RAD10 protein, S cerevisiae
  • Single-Strand Specific DNA and RNA Endonucleases