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PMID: 11027336 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Werner protein recruits DNA polymerase delta to the nucleolus.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 21 ·2000-10-10 ·Pages 11365-70

Szekely AM, Chen YH, Zhang C, Oshima J, Weissman SM

Abstract

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.

MeSH Terms
Biological Transport Cell Nucleolus/enzymology DNA Helicases/metabolism DNA Polymerase III/metabolism Exodeoxyribonucleases HeLa Cells Humans RecQ Helicases Two-Hybrid System Techniques Werner Syndrome/metabolism Werner Syndrome Helicase
Chemicals
DNA Polymerase III Exodeoxyribonucleases DNA Helicases RecQ Helicases WRN protein, human Werner Syndrome Helicase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Szekely A M
Boyer Center for Molecular Medicine and Department of Genetics, Yale University School of Medicine, New Haven CT, 06510, USA.
Chen Y H
Zhang C
Oshima J
Weissman S M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.97.21.11365
Published
2000-10-10
Pages
11365-70
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC17206
Subset
IM
Grants
NCI NIH HHS · CA425566 · United States
NIA NIH HHS · P60-AG-10469 · United States
External Links
PubMed source DOI: 10.1073/pnas.97.21.11365 PMC Full Text View journal details
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