The budding yeast protein Chl1p is required to preserve genome integrity upon DNA damage in S-phase

The budding yeast protein, Chl1p, is required for sister-chromatid cohesion, transcriptional silencing, rDNA recombination and aging. In this work, we show that Chl1p is also required for viability when DNA replication is stressed, either due to mutations or if cells are treated with genotoxic agents like methylmethane sulfonate (MMS) and ultraviolet (UV) rays. The chl1 mutation caused synthetic growth defects with mutations in DNA replication genes. At semi-permissive temperatures, the double mutants grew poorly, were less viable and showed nuclear fragmentation. They were, however, not limited in their bulk DNA synthesis. When chl1 cells were treated with relatively low levels of MMS in S-phase, they lost viability. The S-phase DNA damage checkpoint pathway, however, remained active in these cells. Agarose gel electrophoresis of genomic DNA isolated from wild-type and chl1 cells, after recovery from MMS treatment, suggested that the wild-type was more proficient in the repair of DNA damage than the mutant. Our work suggests that Chl1p is required for genome integrity when cells suffer endogenously or exogenously induced DNA damage