3HUE

Structure of the S. pombe Nbs1 FHA-BRCT1-BRCT2 domains

Summary for 3HUE

• Entry DOI: 10.2210/pdb3hue/pdb
• Related: 3HUF
• Descriptor: DNA repair and telomere maintenance protein nbs1 (2 entities in total)
• Functional Keywords: nbs1, fha domain, brct domain, phosphoprotein binding, phosphoserine binding, dna repair., chromosomal protein, dna damage, dna repair, nucleus, phosphoprotein, telomere, dna binding protein, cell cycle
• Biological source: Schizosaccharomyces pombe (Fission yeast)
• Cellular location: Nucleus: O43070
• Total number of polymer chains: 1
• Total formula weight: 38865.92

Authors

Williams, R.S.,Guenther, G.,Tainer, J.A. (deposition date: 2009-06-13, release date: 2009-10-13, Last modification date: 2024-11-06)

Primary citation

Williams, R.S.,Dodson, G.E.,Limbo, O.,Yamada, Y.,Williams, J.S.,Guenther, G.,Classen, S.,Glover, J.N.,Iwasaki, H.,Russell, P.,Tainer, J.A.
Nbs1 flexibly tethers Ctp1 and Mre11-Rad50 to coordinate DNA double-strand break processing and repair.
Cell(Cambridge,Mass.), 139:87-99, 2009

PubMed Abstract: The Nijmegen breakage syndrome 1 (Nbs1) subunit of the Mre11-Rad50-Nbs1 (MRN) complex protects genome integrity by coordinating double-strand break (DSB) repair and checkpoint signaling through undefined interactions with ATM, MDC1, and Sae2/Ctp1/CtIP. Here, fission yeast and human Nbs1 structures defined by X-ray crystallography and small angle X-ray scattering (SAXS) reveal Nbs1 cardinal features: fused, extended, FHA-BRCT(1)-BRCT(2) domains flexibly linked to C-terminal Mre11- and ATM-binding motifs. Genetic, biochemical, and structural analyses of an Nbs1-Ctp1 complex show Nbs1 recruits phosphorylated Ctp1 to DSBs via binding of the Nbs1 FHA domain to a Ctp1 pThr-Asp motif. Nbs1 structures further identify an extensive FHA-BRCT interface, a bipartite MDC1-binding scaffold, an extended conformational switch, and the molecular consequences associated with cancer predisposing Nijmegen breakage syndrome mutations. Tethering of Ctp1 to a flexible Nbs1 arm suggests a mechanism for restricting DNA end processing and homologous recombination activities of Sae2/Ctp1/CtIP to the immediate vicinity of DSBs.

PubMed: 19804755
DOI: 10.1016/j.cell.2009.07.033

Experimental method

X-RAY DIFFRACTION (2.8 Å)