Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest.
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.
Constantinou
A
A
Clare Hall Laboratories, South Mimms, Herts, UK.
Tarsounas
M
M
Karow
J K
JK
Brosh
R M
RM
Bohr
V A
VA
Hickson
I D
ID
West
S C
SC
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D005090:Exodeoxyribonucleases; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D053484:RecQ Helicases; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D014898:Werner Syndrome / Q000235:genetics / Q000378:metabolism*; D000071657:Werner Syndrome Helicase
D001426:Bacterial Proteins; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate; D004247:DNA; D005090:Exodeoxyribonucleases; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase