WRN interacts physically and functionally with the recombination mediator protein RAD52 |
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Authors: | Baynton Kathy Otterlei Marit Bjørås Magnar von Kobbe Cayetano Bohr Vilhelm A Seeberg Erling |
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Institution: | Centre for Molecular Biology and Neuroscience, and Institute of Medical Microbiology, University of Oslo, Rikshospitalet, 0027 Oslo, Norway. |
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Abstract: | Werner syndrome (WS) is a premature aging disorder that predisposes affected individuals to cancer development. The affected gene, WRN, encodes an RecQ homologue whose precise biological function remains elusive. Altered DNA recombination is a hallmark of WS cells suggesting that WRN plays an important role in these pathways. Here we report a novel physical and functional interaction between WRN and the homologous recombination mediator protein RAD52. Fluorescence resonance energy transfer (FRET) analyses show that WRN and RAD52 form a complex in vivo that co-localizes in foci associated with arrested replication forks. Biochemical studies demonstrate that RAD52 both inhibits and enhances WRN helicase activity in a DNA structure-dependent manner, whereas WRN increases the efficiency of RAD52-mediated strand annealing between non-duplex DNA and homologous sequences contained within a double-stranded plasmid. These results suggest that coordinated WRN and RAD52 activities are involved in replication fork rescue after DNA damage. |
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