NHEJ regulation by mating type is exercised through a novel protein, Lif2p, essential to the ligase IV pathway.
In the yeast Saccharomyces cerevisiae, DNA double strand break (DSB) repair by nonhomologous end-joining (NHEJ) requires the DNA end-binding heterodimer Yku70p-Yku80p and the ligase Dnl4p associated with its cofactor Lif1p. NHEJ efficiency is down-regulated in MATa/MATalpha cells relative to MATa or MATalpha cells, but the mechanism of this mating type ... regulation is unknown. Here we report the identification of Lif2p, a S. cerevisiae protein that interacts with Lif1p in a two-hybrid system. Disruption of LIF2 abolishes the capacity of cells to repair DSBs by end-joining to the same extent than lif1 and dnl4 mutants. In MATa/MATalpha cells, Lif2p steady-state level is strongly repressed when other factors involved in NHEJ are unaffected. Increasing the dosage of the Lif2p protein can suppress the NHEJ defect in a/alpha cells. Together, these results indicate that NHEJ regulation by mating type is achieved, at least in part, by a regulation of Lif2p activity.
Mesh Terms:
Antigens, Nuclear, Base Sequence, Cell Survival, Codon, DNA Damage, DNA Helicases, DNA Ligases, DNA Repair, DNA-Binding Proteins, Dimerization, Down-Regulation, Genotype, Haploidy, Models, Genetic, Molecular Sequence Data, Mutation, Nuclear Proteins, Plasmids, Protein Binding, Protein Structure, Tertiary, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Two-Hybrid System Techniques
Antigens, Nuclear, Base Sequence, Cell Survival, Codon, DNA Damage, DNA Helicases, DNA Ligases, DNA Repair, DNA-Binding Proteins, Dimerization, Down-Regulation, Genotype, Haploidy, Models, Genetic, Molecular Sequence Data, Mutation, Nuclear Proteins, Plasmids, Protein Binding, Protein Structure, Tertiary, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Two-Hybrid System Techniques
Genes Dev.
Date: Nov. 15, 2001
PubMed ID: 11711435
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