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MRE11/RAD50/NBS1: complex activities

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Abstract

The MRE11/RAD50/NBS1 complex (Mre11 complex) is a central player in most aspects of the cellular response to DNA double-strand breaks, including homologous recombination, non-homologous end joining, telomere maintenance and DNA damage checkpoint activation. Several of these findings are explained by the unusual enzymatic activities and macromolecular structure of the Mre11 complex. The Mre11 complex possesses an ATP-stimulated nuclease to process heterogeneous DNA ends and long coiled-coil tails to link DNA ends and/or sister chromatids. However, the mechanistic role of the Mre11 complex in checkpoint activation has been unclear until recently. New data suggest that the Mre11 complex can directly activate the ATM checkpoint kinase at DNA breaks. These findings, together with newly determined functional interactions, identify the Mre11 complex as an architectural and mechanistic keystone of cellular response events emerging from DNA breaks.

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Abbreviations

ABC:

ATP binding cassette

AT:

Ataxia telangiectasia

ATM:

Ataxia telangiectasia mutated

DSB:

DNA double-strand break

dsDNA:

Double-strand DNA

ssDNA:

Single-strand DNA

HR:

Homologous recombination

NBS:

Nijmegen Breakage syndrome

NHEJ:

Non-homologous end joining

WS:

Werner syndrome

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Acknowledgements

We apologize to all colleagues whose key contributions could not been cited due to space restrictions and focus. Work in the laboratory of K.P.H. is supported by a grant from the Deutsche Forschungsgemeinschaft (HO2489/1) and the EMBO young investigator award.

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Correspondence to Karl-Peter Hopfner.

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Communicated by E.A. Nigg

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Assenmacher, N., Hopfner, KP. MRE11/RAD50/NBS1: complex activities. Chromosoma 113, 157–166 (2004). https://doi.org/10.1007/s00412-004-0306-4

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  • DOI: https://doi.org/10.1007/s00412-004-0306-4

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