Characterisation of the interaction between WRN, the helicase/exonuclease defective in progeroid Werner's syndrome, and an essential replication factor, PCNA
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Abstract
Ageing is linked to the accumulation of replicatively senescent cells. The best model
system to date for studying human cellular ageing is the progeroid Werner's syndrome
(WS), caused by a defect in WRN, a recQ-like helicase that also possesses exonuclease
activity. In this paper, we characterise the interaction between WRN and an essential
replication factor, PCNA. We show that wild-type WRN protein physically associates
with PCNA at physiological protein concentrations in normal cells, while no association
is seen in cells from patients with WS. We demonstrate co-localisation of WRN and
PCNA at replication factories, show that PCNA binds to two distinct functional sites
on WRN, and suggest a mechanism by which association between WRN and PCNA may be regulated
in cells on DNA damage and during DNA replication.