期刊
MECHANISMS OF AGEING AND DEVELOPMENT
卷 124, 期 2, 页码 167-174出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/S0047-6374(02)00131-8
关键词
WRN; PCNA; DNA replication; Werner's syndrome; cellular senescence; ageing
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-Iike helicase that also possesses exonuclease activity. In this paper, we characterise the interaction between WRN and an essential replication factor, PCNA. We show that wildtype 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. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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