GM1492 human diploid skin fibroblasts lack the p53-dependent G1 cell-cycle checkpoint.
Recently, we reported that GM1492 human diploid skin fibroblasts derived 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 the cell-cycle. Here we show that in GM1492 cells other types of DNA-damaging agents also fail to induce p53 as well as WAF1, a p53-regulated gene product involved in G1 cell-cycle arrest. Furthermore, the p53-dependent G1 cell-cycle checkpoint is indeed defective in these cells: However, induction of GADD45 mRNA still occurs in GM1492 after irradiation with UV-C. Since GADD45 is known to inhibit the entry into S, these data suggest that the observed accumulation of GM1492 cells in G1 after UV-C irradiation occurs at the G1/S boundary and is due to an inhibition of initiation of DNA-replication.
van Laar
T
T
Laboratory of Molecular Carcinogenesis, Sylvius Laboratories, Leiden University, The Netherlands.
Steegenga
W T
WT
Jochemsen
A G
AG
Terleth
C
C
van der Eb
A J
AJ
D001816:Bloom Syndrome / Q000473:pathology*; D002453:Cell Cycle / Q000528:radiation effects; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004260:DNA Repair; D004261:DNA Replication; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014466:Ultraviolet Rays; D014965:X-Rays; D000097642:GADD45 Proteins
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D000097642:GADD45 Proteins; C493956:CDKN1A protein, human