Journal article

Publication year: 2012

Pages: 693-700

Journal: Nature Structural & Molecular Biology

Volume number: 19

Issue number: 7

ISSN: 1545-9985

DOI Link: https://doi.org/10.1038/nsmb.2323

Publisher: Nature Research

Abstract: 
The Mre11-Rad50-Nbs1 (MRN) complex tethers, processes and signals DNA double-strand breaks, promoting genomic stability. To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1. Two Nbs1 subunits stretch around the outside of the nuclease domains of Mre11, with one subunit additionally bridging and locking the Mre11 dimer via a highly conserved asymmetrical binding motif. Our results show that Mre11 forms a flexible dimer and suggest that Nbs1 not only is a checkpoint adaptor but also functionally influences Mre11-Rad50. Clinical mutations in Mre11 are located along the Nbs1-interaction sites and weaken the Mre11-Nbs1 interaction. However, they differentially affect DNA repair and telomere maintenance in Saccharomyces cerevisiae, potentially providing insight into their different human disease pathologies.

Harvard Citation style: Schiller, C., Lammens, K., Guerini, I., Coordes, B., Feldmann, H., Schlauderer, F., et al. (2012) Structure of Mre11-Nbs1 complex yields insights into ataxia-telangiectasia-like disease mutations and DNA damage signaling, Nature Structural & Molecular Biology, 19(7), pp. 693-700. https://doi.org/10.1038/nsmb.2323

APA Citation style: Schiller, C., Lammens, K., Guerini, I., Coordes, B., Feldmann, H., Schlauderer, F., Möckel, C., Schele, A., Strässer, K., Jackson, S., & Hopfner, K. (2012). Structure of Mre11-Nbs1 complex yields insights into ataxia-telangiectasia-like disease mutations and DNA damage signaling. Nature Structural & Molecular Biology. 19(7), 693-700. https://doi.org/10.1038/nsmb.2323