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-Yku8Op and the ligase Dnl4p associated with its cofactor Lif1p. NHEJ efficiency is down-regulated in MATa/MAT alpha cells relative to MATa or MAT alpha 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 lift and dnl4 mutants. In MATa/MAT alpha 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.