L. Li et al., hRAD17, a structural homolog of the Schizosaccharomyces pombe RAD17 cell cycle checkpoint gene, stimulates p53 accumulation, ONCOGENE, 18(9), 1999, pp. 1689-1699
The RAD17 gene product of S. Pombe is an essential component of the checkpo
int control pathway which responds to both DNA damage and disruption of rep
lication. We have identified a human cDNA that encodes a polypeptide which
is structurally conserved with the S, Pombe Rad17 protein. The human gene,
designated hRAD17, predicts an encoded protein of 590 amino acids and a mol
ecular weight of 69 kD. Amino acid sequence alignment revealed that hRad17
has 28.3% and 52.5% similarity with the S. Pombe Rad17 protein, and 21.8% i
dentity and 45.8% similarity to the budding yeast cell cycle checkpoint pro
tein, Rad 24. When introduced into the S. Pombe rad17 mutant, hRAD17 was ab
le to partially revert its hydroxyurea and ionizing radiation hypersensitiv
ity, but not its UV hypersensitivity. Permanent overexpression of the kRAD1
7 gene in human fibrosarcoma cells resulted in p53 activation and a signifi
cant reduction of S- and G2/M-phase cells accompanied by an accumulation of
the G1-phase population, suggesting that hRAD17 may have a role in cell cy
cle checkpoint control, Immunostaining of HT-1080 cells transiently transfe
cted with a hRAD17 construct confirmed the nuclear accumulation of p53, whi
ch mimics the induction caused by DNA damage. Using FISH analysis, we have
mapped the hRAD17 locus to human chromosome 5q11.2.