Werner's Syndrome Protein (WRN) Migrates Holliday Junctions and Co-localizes with RPA Upon Replication Arrest

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2001 Mar 21

PMID 11256630

Citations 150

Authors

A Constantinou

M Tarsounas

J K Karow

R M Brosh

V A Bohr

I D Hickson

S C West

Affiliations

Soon will be listed here.

Abstract

Individuals affected by the autosomal recessive disorder Werner's syndrome (WS) develop many of the symptoms characteristic of premature ageing. Primary fibroblasts cultured from WS patients exhibit karyotypic abnormalities and a reduced replicative life span. The WRN gene encodes a 3'-5' DNA helicase, and is a member of the RecQ family, which also includes the product of the Bloom's syndrome gene (BLM). In this work, we show that WRN promotes the ATP-dependent translocation of Holliday junctions, an activity that is also exhibited by BLM. In cells arrested in S-phase with hydroxyurea, WRN localizes to discrete nuclear foci that coincide with those formed by the single-stranded DNA binding protein replication protein A. These results are consistent with a model in which WRN prevents aberrant recombination events at sites of stalled replication forks by dissociating recombination intermediates.

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