Werner protein recruits DNA polymerase delta to the nucleolus.
Werner syndrome is a Mendelian disorder of man that produces a number of manifestations resembling human aging. This disorder is caused by inactivation of the wrn gene, a member of the RecQ family of DNA helicases. The helicase and exonuclease activities of the Werner protein (WRN) suggest that it functions in DNA transactions, but the physiological function of WRN remains elusive. We present several lines of evidence that WRN interacts specifically with the p50 subunit of polymerase delta, the major DNA polymerase required for chromosomal DNA replication. P50, identified by yeast two-hybrid screening, interacts physically with the C terminus of WRN. Native WRN protein coimmunoprecipitates with p50 in a cellular fraction enriched in nucleolar proteins, and this immunocomplex also includes p125, the catalytic subunit of polymerase delta. In subcellular localization studies of cells transfected with WRN, p50 and p125 redistribute to the nucleolus and colocalize with WRN. These results suggest that one of the functions of WRN protein is to directly modify DNA replication via its interaction with p50 and abet dynamic relocalization of the DNA polymerase delta complexes within the nucleus.
Szekely
A M
AM
Boyer Center for Molecular Medicine and Department of Genetics, Yale University School of Medicine, New Haven CT, 06510, USA.
Chen
Y H
YH
Zhang
C
C
Oshima
J
J
Weissman
S M
SM
D001692:Biological Transport; D002466:Cell Nucleolus / Q000201:enzymology*; D004265:DNA Helicases / Q000378:metabolism*; D004258:DNA Polymerase III / Q000378:metabolism*; D005090:Exodeoxyribonucleases; D006367:HeLa Cells; D006801:Humans; D053484:RecQ Helicases; D020798:Two-Hybrid System Techniques; D014898:Werner Syndrome / Q000378:metabolism*; D000071657:Werner Syndrome Helicase
D004258:DNA Polymerase III; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase