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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Authors: | Rodríguez-López Ana M Jackson Dean A Nehlin Jan O Iborra Francisco Warren Anna V Cox Lynne S |
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Affiliation: | Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. |
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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. |
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Keywords: | WRN PCNA DNA replication Werner's syndrome Cellular senescence Ageing |
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