Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest
- PMID: 11256630
- PMCID: PMC1083680
- DOI: 10.1093/embo-reports/kvd004
Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest
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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References
-
- Bennett R.J., Keck, J.L. and Wang, J.C. (1999) Binding specificity determines polarity of DNA unwinding by the Sgs1 protein of S. cerevisiae. J. Mol. Biol., 289, 235–248. - PubMed
-
- Brosh R.M., Orren, D.K., Nehlin, J.O., Ravn, P.H., Kenny, M.K., Machwe, A. and Bohr, V.A. (1999) Functional and physical interaction between WRN helicase and human replication protein A. J. Biol. Chem., 274, 18341–18350. - PubMed
-
- Chakraverty R.K. and Hickson, I.D. (1999) Defending genome integrity during DNA replication: a proposed role for RecQ family helicases. BioEssays, 21, 286–294. - PubMed
-
- Eggleston A.K., Mitchell, A.H. and West, S.C. (1997) In vitro reconstitution of the late steps of genetic recombination in E. coli. Cell, 89, 607–617. - PubMed
-
- Epstein C.J., Martin, G.M., Schultz, A.L. and Motulsky, A.G. (1966) Werner’s syndrome: a review of its symptomatology, natural history, pathologic features, genetics and relationship to the natural aging process. Medicine, 45, 177–221. - PubMed
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