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.

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.
Mesh Terms:
Cloning, Molecular, DNA, DNA Damage, DNA Polymerase I, DNA Repair, DNA Replication, Electrophoresis, Gel, Pulsed-Field, Endodeoxyribonucleases, Flap Endonucleases, Mutation, Neoplasm Proteins, Plasmids, Proto-Oncogene Proteins c-bcl-2, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Two-Hybrid System Techniques
Curr. Genet.
Date: Jul. 01, 2005
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