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PROSITE documentation PDOC51131 [for PROSITE entry PS51131]

Rad50 zinc-hook domain profile





Description

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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Technical section

PROSITE method (with tools and information) covered by this documentation:

ZN_HOOK, PS51131; Rad50 zinc-hook domain profile  (MATRIX)


References

1Authorsvan den Bosch M. Bree R.T. Lowndes N.F.
TitleThe MRN complex: coordinating and mediating the response to broken chromosomes.
SourceEMBO Rep. 4:844-849(2003).
PubMed ID12949583
DOI10.1038/sj.embor.embor925

2Authorsde Jager M. van Noort J. van Gent D.C. Dekker C. Kanaar R. Wyman C.
TitleHuman Rad50/Mre11 is a flexible complex that can tether DNA ends.
SourceMol. Cell 8:1129-1135(2001).
PubMed ID11741547

3AuthorsHopfner 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.
TitleThe Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair.
SourceNature 418:562-566(2002).
PubMed ID12152085
DOI10.1038/nature00922



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