HUMAN AND MOUSE HOMOLOGS OF SCHIZOSACCHAROMYCES-POMBE RAD1(-CEREVISIAE RAD17 - LINKAGE TO CHECKPOINT CONTROL AND MAMMALIAN MEIOSIS() AND SACCHAROMYCES)

preventing or delaying progress through the cell cycle in response to DNA damage is crucial for eukaryotic cells to allow the damage to be r epaired and not incorporated irrevocably into daughter cells. Several genes involved in this process have been discovered in fission and bud ding yeast. Here, rye report the identification of human and mouse hom ologs of the Schizosaccharomyces pombe DNA damage checkpoint control g ene rad1(+) and its Saccharomyces cerevisiae homolog RAD17. The human gene HRAD1 is located on chromosome 5p13 and is most homologous to S. pombe rad1(+). This gene encodes a 382-amino-acid residue protein that is localized mainly in the nucleus and is expressed at high levels in proliferative tissues. This human gene significantly complements the sensitivity to UV light of a S. pombe strain mutated in rad1(+). Moreo ver, HRAD1 complements the checkpoint control defect of this strain af ter UV exposure. In addition to functioning in DNA repair checkpoints, S. cerevisiae RAD17 plays a role during meiosis to prevent progress t hrough prophase I when recombination is interrupted. Consistent with a Similar role in mammals. Rad1. protein is abundant in testis, and is associated with both synapsed and unsynapsed chromosomes during meioti c prophase I of spermatogenesis, with a staining pattern distinct from that of the recombination proteins Rad51 and Dmc1. Together, these da ta imply an important role for hRad1 both in the mitotic DNA damage ch eckpoint and in meiotic checkpoint mechanisms, and suggest that these events are highly conserved from yeast to humans.