RAD1,a Human Structural Homolog of theSchizosaccharomyces pombe RAD1Cell Cycle Checkpoint Gene

Cell cycle checkpoints are gating mechanisms that govern cell cycle progression in the presence of DNA damage and incomplete DNA replication. TheSchizosaccharomyces pombeRad1 protein is an essential component of cell cycle checkpoints activated by both types of genomic stress. In this study, we report the isolation of a human homolog of theS. pombe RAD1gene. The hRAD1 protein is also similar to theSaccharomyces cerevisiaecell cycle checkpoint protein Rad17 and theUstilago maydis3′ → 5′ exonuclease, Rec1. We show that humanRAD1partially complements the hydroxyurea and ionizing radiation hypersensitivities of aS. pombe rad1mutant, suggesting phylogenetic conservation of the DNA damage and replication checkpoints. The humanRAD1locus was mapped to human chromosome 5p13.2, a locus frequently altered in non-small-cell lung cancer and bladder cancer.