title: Characterisation of the interaction between WRN, the helicase/exonuclease defective in progeroid Werner's syndrome, and an essential replication factor, PCNA.
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.
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Rodríguez-López
authors.forename: Dean A
authors.initials: DA
authors.lastname: Jackson
authors.forename: Jan O
authors.initials: JO
authors.lastname: Nehlin
authors.forename: Francisco
authors.initials: F
authors.lastname: Iborra
authors.forename: Anna V
authors.initials: AV
authors.lastname: Warren
authors.forename: Lynne S
authors.initials: LS
authors.lastname: Cox
mesh_terms: D000595:Amino Acid Sequence; D016922:Cellular Senescence / Q000502:physiology; D002874:Chromosome Mapping; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism*; D004261:DNA Replication / Q000502:physiology; D005090:Exodeoxyribonucleases; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D053484:RecQ Helicases; D016196:S Phase / Q000502:physiology; D014898:Werner Syndrome / Q000235:genetics* / Q000378:metabolism*; D000071657:Werner Syndrome Helicase
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase