GM1492 HUMAN-DIPLOID SKIN FIBROBLASTS LACK THE P53-DEPENDENT G1 CELL-CYCLE CHECKPOINT

Recently, we reported that GM1492 human diploid skin fibroblasts deriv ed from a Bloom's. patient upon UV-C irradiation fail to increase p53 to a detectable level and nevertheless accumulate in the G1-phase of t he cell-cycle, Here we show that in GM1492 cells other types of DNA-da maging agents also fail to induce p53 as well as WAF1, a p53-regulated gene product involved in G1 cell-cycle arrest, Furthermore, the p53-d ependent G1 cell-cycle checkpoint is indeed defective in these cells. However, induction of GADD45 mRNA still occurs in GM1492 after irradia tion with UV-C, Since GADD45 is known to inhibit the entry into S, the se data suggest that the observed accumulation of GM1492 cells in G1 a fter W-C irradiation occurs at the G1/S boundary and is due to an inhi bition of initiation of DNA-replication. (C) 1995 Academic Press, Inc.