Rad62 protein functionally and physically associates with the smc5/smc6 protein complex and is required for chromosome integrity and recombination repair in fission yeast

Mol Cell Biol. 2004 Nov;24(21):9401-13. doi: 10.1128/MCB.24.21.9401-9413.2004.

Abstract

Smc5 and Smc6 proteins form a heterodimeric SMC (structural maintenance of chromosome) protein complex like SMC1-SMC3 cohesin and SMC2-SMC4 condensin, and they associate with non-SMC proteins Nse1 and Nse2 stably and Rad60 transiently. This multiprotein complex plays an essential role in maintaining chromosome integrity and repairing DNA double strand breaks (DSBs). This study characterizes a Schizosaccharomyces pombe mutant rad62-1, which is hypersensitive to methyl methanesulfonate (MMS) and synthetically lethal with rad2 (a feature of recombination mutants). rad62-1 is hypersensitive to UV and gamma rays, epistatic with rhp51, and defective in repair of DSBs. rad62 is essential for viability and genetically interacts with rad60, smc6, and brc1. Rad62 protein physically associates with the Smc5-6 complex. rad62-1 is synthetically lethal with mutations in the genes promoting recovery from stalled replication, such as rqh1, srs2, and mus81, and those involved in nucleotide excision repair like rad13 and rad16. These results suggest that Rad62, like Rad60, in conjunction with the Smc5-6 complex, plays an essential role in maintaining chromosome integrity and recovery from stalled replication by recombination.

MeSH terms

  • Base Sequence
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosomes, Fungal / metabolism*
  • Cloning, Molecular
  • DNA Damage
  • DNA Repair* / radiation effects
  • DNA Replication
  • DNA, Fungal / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Epistasis, Genetic
  • Genes, Essential / genetics
  • Genes, Fungal / genetics
  • Molecular Sequence Data
  • Multiprotein Complexes
  • Mutation / genetics
  • Protein Binding
  • Rad51 Recombinase
  • Recombination, Genetic* / genetics
  • Recombination, Genetic* / radiation effects
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / growth & development
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Sequence Alignment

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA, Fungal
  • DNA-Binding Proteins
  • Multiprotein Complexes
  • Nse4 protein, S pombe
  • RHP51 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • Smc5 protein, S pombe
  • smc6 protein, S pombe
  • Rad51 Recombinase

Associated data

  • GENBANK/AB158548