Genetic control of telomere integrity in Schizosaccharomyces pombe: rad3(+) and tel1(+) are parts of two regulatory networks independent of the downstream protein kinases chk1(+) and cds1(+)

Genetics. 1999 Aug;152(4):1501-12. doi: 10.1093/genetics/152.4.1501.

Abstract

The Schizosaccharomyces pombe checkpoint gene named rad3(+) encodes an ATM-homologous protein kinase that shares a highly conserved motif with proteins involved in DNA metabolism. Previous studies have shown that Rad3 fulfills its function via the regulation of the Chk1 and Cds1 protein kinases. Here we describe a novel role for Rad3 in the control of telomere integrity. Mutations in the rad3(+) gene alleviated telomeric silencing and produced shortened lengths in the telomere repeat tracts. Genetic analysis revealed that the other checkpoint rad mutations rad1, rad17, and rad26 belong to the same phenotypic class with rad3 with regard to control of the telomere length. Of these mutations, rad3 and rad26 have a drastic effect on telomere shortening. tel1(+), another ATM homologue in S. pombe, carries out its telomere maintenance function in parallel with the checkpoint rad genes. Furthermore, either a single or double disruption of cds1(+) and chk1(+) caused no obvious changes in the telomeric DNA structure. Our results demonstrate a novel role of the S. pombe ATM homologues that is independent of chk1(+) and cds1(+).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / physiology*
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins*
  • Checkpoint Kinase 1
  • Checkpoint Kinase 2
  • Chromosomes, Fungal / ultrastructure*
  • DNA Helicases / genetics
  • DNA Helicases / physiology*
  • DNA-Binding Proteins
  • Fungal Proteins / genetics*
  • Fungal Proteins / physiology*
  • Orotic Acid / analogs & derivatives
  • Orotic Acid / pharmacology
  • Protein Kinases / physiology*
  • Protein Serine-Threonine Kinases*
  • Proteins / physiology
  • Radiation Tolerance / genetics
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces / drug effects
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces / ultrastructure
  • Schizosaccharomyces pombe Proteins*
  • Signal Transduction / physiology*
  • Telomere / ultrastructure*
  • Tumor Suppressor Proteins

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Fungal Proteins
  • Proteins
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces pombe Proteins
  • Tumor Suppressor Proteins
  • rad26 protein, S pombe
  • Orotic Acid
  • 5-fluoroorotic acid
  • Protein Kinases
  • Checkpoint Kinase 2
  • Ataxia Telangiectasia Mutated Proteins
  • Cds1 protein, S pombe
  • Checkpoint Kinase 1
  • Chk1 protein, S pombe
  • Protein Serine-Threonine Kinases
  • tel1 protein, S pombe
  • Adenosine Triphosphatases
  • Rad3 protein, S cerevisiae
  • DNA Helicases