Angelos Constantinou1, Madalena Tarsounas1, Julia Karow2, Robert Brosh3, Vilhelm A. Bohr3, Ian D. Hickson2, Stephen C. West1
1Imperial Cancer Research Fund, Clare Hall Laboratories Blanche Lane, South Mimms Herts EN6 3LD UK
2ICRF Laboratories, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital Oxford OX3 9DS UK
3Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health Baltimore MD 21224 USA
Tóm tắt
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.
