Suppression of spontaneous chromosomal rearrangements by S phase checkpoint functions in Saccharomyces cerevisiae

Cell. 2001 Feb 9;104(3):397-408. doi: 10.1016/s0092-8674(01)00227-6.

Abstract

Cancer cells show increased genome rearrangements, although it is unclear what defects cause these rearrangements. Mutations in Saccharomyces cerevisiae RFC5, DPB11, MEC1, DDC2 MEC3, RAD53, CHK1, PDS1, and DUN1 increased the rate of genome rearrangements up to 200-fold whereas mutations in RAD9, RAD17, RAD24, BUB3, and MAD3 had little effect. The rearrangements were primarily deletion of a portion of a chromosome arm along with TEL1-dependent addition of a new telomere. tel1 mutations increased the proportion of translocations observed, and in some cases showed synergistic interactions when combined with mutations that increased the genome rearrangement rate. These data suggest that one role of S phase checkpoint functions in normal cells is to suppress spontaneous genome rearrangements resulting from DNA replication errors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Chromosome Deletion
  • Chromosomes / genetics*
  • DNA Damage
  • DNA Replication
  • Endodeoxyribonucleases*
  • Exodeoxyribonucleases*
  • Fungal Proteins / metabolism
  • Fungal Proteins / physiology
  • Genotype
  • Intracellular Signaling Peptides and Proteins
  • Models, Genetic
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Mutation
  • Protein-Serine-Threonine Kinases
  • S Phase*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Nucleic Acid
  • Signal Transduction
  • Suppression, Genetic*
  • Telomere / physiology*
  • Translocation, Genetic

Substances

  • Fungal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Saccharomyces cerevisiae Proteins
  • MEC1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • TEL1 protein, S cerevisiae
  • Endodeoxyribonucleases
  • Exodeoxyribonucleases
  • MRE11 protein, S cerevisiae