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EMBO reports 4, 9, 844–849 (2003)
doi:10.1038/sj.embor.embor925
The MRN complex: coordinating and mediating the response to broken chromosomes
Michael van den Bosch, Ronan T. Bree & Noel F. Lowndes
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Genome Stability Laboratory, Department of Biochemistry and National Centre for Biomedical Engineering Science, National University of Ireland Galway, University Road, Galway, Ireland
To whom correspondence should be addressed
Noel F. Lowndes Tel: + 353 91 750 309; Fax: + 353 91 512 504; noel.lowndes@nuigalway.ie
Received 10 June 2002; Accepted 22 July 2003.
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Abstract
The MRE11–RAD50–NBS1 (MRN) protein complex has been linked to many DNA metabolic events that involve DNA double-stranded breaks (DSBs). In vertebrate cells, all three components are encoded by essential genes, and hypomorphic mutations in any of the human genes can result in genome-instability syndromes. MRN is one of the first factors to be localized to the DNA lesion, where it might initially have a structural role by tethering together, and therefore stabilizing, broken chromosomes. This suggests that MRN could function as a lesion-specific sensor. As well as binding to DNA, MRN has other roles in both the processing and assembly of large macromolecular complexes (known as foci) that facilitate efficient DSB responses. Recently, a novel mediator protein, mediator of DNA damage checkpoint protein 1 (MDC1), was shown to co-immunoprecipitate with the MRN complex and regulate MRE11 foci formation. However, whether the initial recruitment of MRN to DSBs requires MDC1 is unclear. Here, we focus on recent developments in MRN research and propose a model for how DSBs are sensed and the cellular responses to them are mediated.
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