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Vol. 12, Issue 8, 2412-2421, August 2001
Laboratorio di Citogenetica Molecolare e Mutagenesi, DABAC,
Università degli Studi della Tuscia, 01100 Viterbo, Italy
Werner's syndrome (WS) is a rare autosomal recessive disorder that
arises as a consequence of mutations in a gene coding for a protein
that is a member of RecQ family of DNA helicases, WRN. The cellular
function of WRN is still unclear, but on the basis of the cellular
phenotypes of WS and of RecQ yeast mutants, its possible role in
controlling recombination and/or in maintenance of genomic integrity
during S-phase has been envisaged. With the use of two drugs,
camptothecin and hydroxyurea, which produce replication-associated DNA
damage and/or inhibit replication fork progression, we find that WS
cells have a slower rate of repair associated with DNA damage induced
in the S-phase and a reduced induction of RAD51 foci. As a consequence,
WS cells undergo apoptotic cell death more than normal cells, even if
they arrest and resume DNA synthesis at an apparently normal rate.
Furthermore, we report that WS cells show a higher background level of
DNA strand breaks and an elevated spontaneous induction of RAD51 foci.
Our findings support the hypothesis that WRN could be involved in the
correct resolution of recombinational intermediates that arise from
replication arrest due to either DNA damage or replication fork collapse.
These authors contributed equally to this study.
Corresponding author. E-mail address:
palitti{at}unitus.it.
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