RAD1, a human structural homolog of the Schizosaccharomyces pombe RAD1 cell cycle checkpoint gene

Cell cycle checkpoints are gating mechanisms that govern cell cycle progression in the presence of DNA damage and incomplete DNA replication. The Schizosaccharomyces pombe Rad1 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 the S. pombe RAD1 gene. The hRAD1 protein is also similar to the Saccharomyces cerevisiae cell cycle checkpoint protein Rad17 and the Ustilago maydis 3' → 5' exonuclease, Rec1. We show that human RAD1 partially complements the hydroxyurea and ionizing radiation hypersensitivities of a S. pombe rad1 mutant, suggesting phylogenetic conservation of the DNA damage and replication checkpoints. The human RAD1 locus was mapped to human chromosome 5p13.2, a locus frequently altered in nonsmall-cell lung cancer and bladder cancer.