Genetic and physical interactions between Schizosaccharomyces pombe Mcl1 and Rad2, Dna2 and DNA polymerase alpha: evidence for a multifunctional role of Mcl1 in DNA replication and repair

Curr Genet. 2005 Jul;48(1):34-43. doi: 10.1007/s00294-005-0584-2. Epub 2005 May 25.


Schizosaccharomyces pombe rad2 is involved in Okazaki fragments processing during lagging-strand DNA replication. Previous studies identified several slr mutants that are co-lethal with rad2Delta and sensitive to methyl methanesulfonate as single mutants. One of these mutants, slr3-1, is characterized here. Complementation and sequence analyses show that slr3-1 (mcl1-101) is allelic to mcl1(+), which is required for chromosome replication, cohesion and segregation. mcl1-101 is temperature-sensitive for growth and is highly sensitive to DNA damage. mcl1 cells arrest with 2C DNA content and chromosomal DNA double-strand breaks accumulate at the restrictive temperature. Mcl1p, which belongs to the Ctf4p/SepBp family, interacts both genetically and physically with DNA polymerase alpha. Mutations in rhp51 and dna2 enhance the growth defect of the mcl1-101 mutant. These results strongly suggest that Mcl1p is a functional homologue of Saccharomyces cerevisiae Ctf4p and plays a role in lagging-strand synthesis and Okazaki fragment processing, in addition to DNA repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cloning, Molecular
  • DNA
  • DNA Damage
  • DNA Polymerase I / genetics*
  • DNA Polymerase I / metabolism
  • DNA Repair / physiology*
  • DNA Replication / physiology*
  • Electrophoresis, Gel, Pulsed-Field
  • Endodeoxyribonucleases / genetics*
  • Endodeoxyribonucleases / metabolism
  • Flap Endonucleases / genetics*
  • Flap Endonucleases / physiology
  • Mutation
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Plasmids
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / genetics
  • Two-Hybrid System Techniques


  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins
  • Okazaki fragments
  • Proto-Oncogene Proteins c-bcl-2
  • Schizosaccharomyces pombe Proteins
  • DNA
  • DNA Polymerase I
  • Dna2 protein, S pombe
  • Endodeoxyribonucleases
  • Flap Endonucleases
  • Rad2 protein, S pombe