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Nat Struct Mol Biol. 2011 Apr;18(4):423-31. doi: 10.1038/nsmb.2038. Epub 2011 Mar 27.

ABC ATPase signature helices in Rad50 link nucleotide state to Mre11 interface for DNA repair.

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1
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.

Erratum in

  • Nat Struct Mol Biol. 2012 Mar;19(3):364.
  • Nat Struct Mol Biol. 2011 Sep;18(9):1084.

Abstract

The Rad50 ABC-ATPase complex with Mre11 nuclease is essential for dsDNA break repair, telomere maintenance and ataxia telangiectasia-mutated kinase checkpoint signaling. How Rad50 affects Mre11 functions and how ABC-ATPases communicate nucleotide binding and ligand states across long distances and among protein partners are questions that have remained obscure. Here, structures of Mre11-Rad50 complexes define the Mre11 2-helix Rad50 binding domain (RBD) that forms a four-helix interface with Rad50 coiled coils adjoining the ATPase core. Newly identified effector and basic-switch helix motifs extend the ABC-ATPase signature motif to link ATP-driven Rad50 movements to coiled coils binding Mre11, implying an ~30-Å pull on the linker to the nuclease domain. Both RBD and basic-switch mutations cause clastogen sensitivity. Our new results characterize flexible ATP-dependent Mre11 regulation, defects in cancer-linked RBD mutations, conserved superfamily basic switches and motifs effecting ATP-driven conformational change, and they provide a unified comprehension of ABC-ATPase activities.

PMID:
21441914
PMCID:
PMC3118400
DOI:
10.1038/nsmb.2038
[Indexed for MEDLINE]
Free PMC Article
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