Document Detail

Characterisation of the interaction between WRN, the helicase/exonuclease defective in progeroid Werner's syndrome, and an essential replication factor, PCNA.
MedLine Citation:
PMID:  12633936     Owner:  NLM     Status:  MEDLINE    
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.
Ana M Rodríguez-López; Dean A Jackson; Jan O Nehlin; Francisco Iborra; Anna V Warren; Lynne S Cox
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Mechanisms of ageing and development     Volume:  124     ISSN:  0047-6374     ISO Abbreviation:  Mech. Ageing Dev.     Publication Date:  2003 Feb 
Date Detail:
Created Date:  2003-03-13     Completed Date:  2003-12-15     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0347227     Medline TA:  Mech Ageing Dev     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  167-74     Citation Subset:  IM    
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
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MeSH Terms
Amino Acid Sequence
Cell Aging / physiology
Chromosome Mapping
DNA Helicases / genetics*,  metabolism*
DNA Replication / physiology
Hela Cells
Molecular Sequence Data
Proliferating Cell Nuclear Antigen / genetics*,  metabolism*
Protein Binding / physiology
RecQ Helicases
S Phase / physiology
Werner Syndrome / genetics*,  metabolism*
Reg. No./Substance:
0/Proliferating Cell Nuclear Antigen; EC 3.1.-/Exodeoxyribonucleases; EC 3.6.1.-/DNA Helicases; EC 3.6.1.-/RecQ Helicases; EC 3.6.1.-/WRN protein, human

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