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* Residue conservation analysis
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PDB id:
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Gene regulation/antitumor protein
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Title:
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Crystal structure of a rad51-brca2 brc repeat complex
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Structure:
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DNA repair protein rad51 homolog 1. Chain: a. Fragment: atpase domain. Synonym: rad51, hrad51, hsrad51. Engineered: yes. Breast cancer type 2 susceptibility protein. Chain: b. Fragment: brc repeat type 4. Synonym: brca2 brc4 repeat sequence.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: rad51. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: brca2.
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Biol. unit:
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Tetramer (from
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Resolution:
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1.70Å
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R-factor:
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0.191
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R-free:
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0.206
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Authors:
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L.Pellegrini,D.S.Yu,T.Lo,S.Anand,M.Lee,T.L.Blundell,A.R.Venkitaraman
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Key ref:
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L.Pellegrini
et al.
(2002).
Insights into DNA recombination from the structure of a RAD51-BRCA2 complex.
Nature,
420,
287-293.
PubMed id:
DOI:
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Date:
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15-Oct-02
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Release date:
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27-Nov-02
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PROCHECK
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Headers
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References
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DOI no:
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Nature
420:287-293
(2002)
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PubMed id:
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Insights into DNA recombination from the structure of a RAD51-BRCA2 complex.
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L.Pellegrini,
D.S.Yu,
T.Lo,
S.Anand,
M.Lee,
T.L.Blundell,
A.R.Venkitaraman.
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ABSTRACT
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The breast cancer susceptibility protein BRCA2 controls the function of RAD51, a
recombinase enzyme, in pathways for DNA repair by homologous recombination. We
report here the structure of a complex between an evolutionarily conserved
sequence in BRCA2 (the BRC repeat) and the RecA-homology domain of RAD51. The
BRC repeat mimics a motif in RAD51 that serves as an interface for
oligomerization between individual RAD51 monomers, thus enabling BRCA2 to
control the assembly of the RAD51 nucleoprotein filament, which is essential for
strand-pairing reactions during DNA recombination. The RAD51 oligomerization
motif is highly conserved among RecA-like recombinases, highlighting a common
evolutionary origin for the mechanism of nucleoprotein filament formation,
mirrored in the BRC repeat. Cancer-associated mutations that affect the BRC
repeat disrupt its predicted interaction with RAD51, yielding structural insight
into mechanisms for cancer susceptibility.
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Selected figure(s)
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Figure 1.
Figure 1: The RAD51 -BRC4 complex. a, Ribbon representation.
RAD51 is in magenta ( -helices)
and light blue ( -strands),
the BRC repeat motif is in green. The N and C termini are
indicated. b, Topology diagram. The colour scheme is the same as
in a, except for the N-terminal strand-helix-strand motif of
RAD51 (yellow). Labelled secondary structure elements in RAD51
constitute the RecA-homology domain. Disordered RAD51 loops
(dashed lines) connect -strand
B4 to -helix
A5 (L1) and B5 to B6 (L2). c, Stereo diagram superposing the
ATPase domains of human RAD51 and bacterial RecA (Protein Data
Bank accession code 2reb). Secondary structure elements are
coloured red (RAD51) or green (RecA).
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Figure 2.
Figure 2: The RAD51 -BRC4 interface. a, Hydrophobic
interactions mediated by the -helical
region of the BRC repeat. RAD51 is rendered as a
solvent-accessible molecular surface (green). The BRC motif is
shown as a maroon coil, featuring only the relevant side chains
(light brown). b, Hydrophobic interactions involving the -hairpin
region of the BRC repeat. c, Polar interactions. RAD51 is shown
in ribbon representation (colouring as in Fig. 1a), and the BRC
motif is shown as a green tube. Interacting side chains are
drawn in stick representation. Dotted yellow lines represent
hydrogen bonds.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2002,
420,
287-293)
copyright 2002.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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PDB codes:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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}
}
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