In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 97, No. 21 ( 2000-10-10), p. 11365-11370
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 δ, 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 δ. 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 δ complexes within the nucleus.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.97.21.11365
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2000
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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