Characterisation of the interaction between WRN, the helicase/exonuclease defective in progeroid Werner's syndrome, and an essential replication factor, PCNA.
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.
Rodríguez-López
Ana M
AM
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Jackson
Dean A
DA
Nehlin
Jan O
JO
Iborra
Francisco
F
Warren
Anna V
AV
Cox
Lynne S
LS
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
D018809:Proliferating Cell Nuclear Antigen; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase