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Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51
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Published on: February 13, 2019

Structural biochemistry and interaction architecture of the DNA double-strand break repair Mre11 nuclease and

K P Hopfner1, A Karcher, L Craig

  • 1Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Cell
|May 24, 2001
PubMed

Insights

We determined crystal structures of the Mre11/Rad50 complex, revealing its DNA repair mechanism. This structure clarifies how the complex processes DNA double-strand breaks.

Area of Science:

  • Structural biology
  • Molecular biology
  • Biochemistry

Background:

  • The Mre11/Rad50 (MR) complex is crucial for DNA double-strand break repair.
  • Understanding the MR complex's structure is key to elucidating its function in DNA repair pathways.

Purpose of the Study:

  • To determine the crystal structures of Pyrococcus furiosus Mre11 and Rad50.
  • To elucidate the structural basis of the Mre11/Rad50 complex's DNA double-strand break repair functions.

Main Methods:

  • X-ray crystallography
  • Electron microscopy
  • Small-angle X-ray scattering
  • Analytical ultracentrifugation

Main Results:

  • Revealed a protein phosphatase-like, dimanganese binding domain in Mre11 controlling active site access.
  • Unified Mre11's nuclease activities into a single endo/exonuclease mechanism.
  • Defined a compact Mre11/Rad50-ATPase complex structure.
  • Identified a dual functional complex with a (Mre11)2/(Rad50)2 heterotetrameric DNA processing head and a coiled-coil linker.

Conclusions:

  • The determined structures provide a mechanistic understanding of Mre11/Rad50 complex in DNA repair.
  • Structural insights reveal eukaryotic macromolecular interaction sites and potential mutation targets.
  • Rad50-ATP-driven conformational changes likely regulate Mre11 exonuclease activity.

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