Carcinogenesis, Vol 19, 2115-2120, Copyright © 1998 by Oxford University Press
M Collister, DP Lane and BL Kuehl
The Bloom's syndrome gene, BLM, encodes a protein which bears homology to
the RecQ helicases. It is believed to be involved in DNA replication and
has been implicated in the maintenance of genomic stability. To investigate
whether BLM was involved in cellular responses to DNA damage Bloom's
syndrome fibroblasts were treated with either UV or ionizing radiation and
the levels of p53 and two of its down stream effectors, p21waf1/cip1 and
hdm2, were determined by western blot analysis. Following 20 J/m2
UVC-radiation we observed that the maximal accumulation of p21waf1/cip1 and
hdm2 proteins preceded that of p53 in both a normal diploid fibroblast cell
strain (GM0038) and in two Bloom's syndrome cell strains. Furthermore, the
Bloom's syndrome cells demonstrated a delayed and prolonged accumulation of
all three proteins and a delayed recovery of the protein levels back to
pre-damage levels compared with the normal cell strain. Conversely, normal
and Bloom's syndrome cell response following 2.5 Gy of ionizing radiation
was quite similar for p21waf1/cip1 and hdm2, but differed significantly for
p53. Maximum accumulation of p53 occurred within 2 h of damage and preceded
that of p21waf1/cip1 and hdm2. These results suggest that the BLM protein
may play a role in the detection of certain types of DNA damage and in the
cellular response to that damage.
ARTICLES
Differential expression of p53, p21waf1/cip1 and hdm2 dependent on DNA damage in Bloom's syndrome fibroblasts
ICRF Laboratories, Pharmacology Unit, Biomedical Research Centre, Ninewells Hospital, Dundee, Scotland.
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