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van den Bosch, M,Bree, RT,Lowndes, NF
2003
September
The MRN complex: coordinating and mediating the response to broken chromosomes
Published
1
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STRAND BREAK REPAIR DNA-DAMAGE CHECKPOINT S-PHASE CHECKPOINT DEPENDENT NUCLEAR-DYNAMICS HISTONE H2AX MRE11 COMPLEX SACCHAROMYCES-CEREVISIAE HOMOLOGOUS RECOMBINATION TARGETED DISRUPTION HUMAN RAD50/MRE11
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.
844
849
DOI 10.1038/sj.embor.embor925
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