{PDOC51131}
{PS51131; ZN_HOOK}
{BEGIN}
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* Rad50 zinc-hook domain profile *
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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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: June 2005 / First entry.

[ 1] van den Bosch M., Bree R.T., Lowndes N.F.
     "The MRN complex: coordinating and mediating the response to broken
     chromosomes."
     EMBO Rep. 4:844-849(2003).
     PubMed=12949583; DOI=10.1038/sj.embor.embor925
[ 2] de Jager M., van Noort J., van Gent D.C., Dekker C., Kanaar R.,
     Wyman C.
     "Human Rad50/Mre11 is a flexible complex that can tether DNA ends."
     Mol. Cell 8:1129-1135(2001).
     PubMed=11741547
[ 3] 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.
     "The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA
     recombination and repair."
     Nature 418:562-566(2002).
     PubMed=12152085; DOI=10.1038/nature00922

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