PROSITE documentation PDOC51131Rad50 zinc-hook domain profile
The MRN complex (Mre11-Rad50-Nbs1) plays an important role in many DNA metabolic events that involve DNA double-stranded breaks. MRN is one of the first factors to be localized to DNA lesions where it might have a structural role by tethering and stabilizing broken chromosomes [1,2].
Rad50 is a split ABC-type ATPase; its center contains a long heptad repeat that folds into an antiparallel coiled coil, bringing the N-terminal (Walker A) and the C-terminal (Walker B) domains in close proximity (see <PDB:1L8D>) [3]. The apex of the coiled coil contains a dimerization interface, a conserved Cys-x-x-Cys motif in a hook-shaped domain that dimerizes with a second hook domain via cysteine-mediated zinc ion coordination (see the schematic representation below). This zinc dependent dimerization event allows the formation of a complex that has appropriate lenghts and conformational proporties to link sister chromatids in homologous recombination and DNA ends in non-homologous end-joining.
x x x x x x x x x x x x
x x x x C C x x x x
x x x x x \ / x x x x x
x x x Zn x x x
x x x x x / \ x x x x x
x x x x C C x x x x
x x x x x x x x x x x x
coiled coil coiled coil
'C': conserved cysteine involved in zinc binding.
The profile we developed covers the two cysteines and the coiled coil region.
Last update:June 2005 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | van den Bosch M. Bree R.T. Lowndes N.F. |
| Title | The MRN complex: coordinating and mediating the response to broken chromosomes. | |
| Source | EMBO Rep. 4:844-849(2003). | |
| PubMed ID | 12949583 | |
| DOI | 10.1038/sj.embor.embor925 |
| 2 | Authors | de Jager M. van Noort J. van Gent D.C. Dekker C. Kanaar R. Wyman C. |
| Title | Human Rad50/Mre11 is a flexible complex that can tether DNA ends. | |
| Source | Mol. Cell 8:1129-1135(2001). | |
| PubMed ID | 11741547 |
| 3 | Authors | Hopfner K.P. Craig L. Moncalian G. Zinkel R.A. Usui T. Owen B.A. Karcher A. Henderson B. Bodmer J.L. McMurray C.T. Carney J.P. Petrini J.H. Tainer J.A. |
| Title | The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair. | |
| Source | Nature 418:562-566(2002). | |
| PubMed ID | 12152085 | |
| DOI | 10.1038/nature00922 |
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