Acta Crystallographica Section D

Biological Crystallography

Volume 70, Part 2 (February 2014)


research papers



Acta Cryst. (2014). D70, 299-309    [ doi:10.1107/S139900471302693X ]

Structural basis for DNA recognition and nuclease processing by the Mre11 homologue SbcD in double-strand breaks repair

S. Liu, L. Tian, Y. Liu, X. An, Q. Tang, X. Yan and D. Liang

Abstract: The Mre11 complex comprising meiotic recombination 11 (Mre11), Rad50 and Nijmegen breakage syndrome 1 (Nbs1) plays multiple important roles in the sensing, processing and repair of DNA double-strand breaks (DSBs). Here, crystal structures of the Escherichia coli Mre11 homologue SbcD and its Mn2+ complex are reported. Dimerization of SbcD depends on a four-helix bundle consisting of helices [alpha]2, [alpha]3, [alpha]2' and [alpha]3' of the two monomers, and the irregular and bent conformation of helices [alpha]3 and [alpha]3' in the SbcD dimer results in a dimeric arrangement that differs from those of previously reported Mre11 dimers. This finding indicates a distinct selectivity in DNA substrate recognition. The biochemical data combined with the crystal structures revealed that the SbcD monomer exhibits single-stranded DNA (ssDNA) endonuclease activity and double-stranded DNA (dsDNA) exonuclease activity on the addition of a high concentration of Mn2+. For the first time, atomic force microscopy analysis has been used to demonstrate that the SbcD monomer also possesses Mn2+-dependent dsDNA endonuclease activity. Loop [beta]7-[alpha]6 of SbcD is likely to be a molecular switch and plays an important role in the regulation of substrate binding, catalytic reaction and state transitions. Based on structural and mutational analyses, a novel ssDNA-binding model of SbcD is proposed, providing insight into the catalytic mechanism of DSBs repair by the Mre11 complex.

PDB references: 4lty and 4m0v

Keywords: DSBs repair; Mre11 protein; Mn2+-dependent nucleases.


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