1miu: Difference between revisions
New page: left|200px<br /> <applet load="1miu" size="450" color="white" frame="true" align="right" spinBox="true" caption="1miu, resolution 3.1Å" /> '''Structure of a BRCA2... |
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[[Image:1miu.gif|left|200px]]<br /> | [[Image:1miu.gif|left|200px]]<br /><applet load="1miu" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1miu, resolution 3.1Å" /> | caption="1miu, resolution 3.1Å" /> | ||
'''Structure of a BRCA2-DSS1 complex'''<br /> | '''Structure of a BRCA2-DSS1 complex'''<br /> | ||
==Overview== | ==Overview== | ||
Mutations in the BRCA2 (breast cancer susceptibility gene 2) tumor | Mutations in the BRCA2 (breast cancer susceptibility gene 2) tumor suppressor lead to chromosomal instability due to defects in the repair of double-strand DNA breaks (DSBs) by homologous recombination, but BRCA2's role in this process has been unclear. Here, we present the 3.1 angstrom crystal structure of a approximately 90-kilodalton BRCA2 domain bound to DSS1, which reveals three oligonucleotide-binding (OB) folds and a helix-turn-helix (HTH) motif. We also (i) demonstrate that this BRCA2 domain binds single-stranded DNA, (ii) present its 3.5 angstrom structure bound to oligo(dT)9, (iii) provide data that implicate the HTH motif in dsDNA binding, and (iv) show that BRCA2 stimulates RAD51-mediated recombination in vitro. These findings establish that BRCA2 functions directly in homologous recombination and provide a structural and biochemical basis for understanding the loss of recombination-mediated DSB repair in BRCA2-associated cancers. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1MIU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with HG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1MIU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=HG:'>HG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MIU OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Chen, P | [[Category: Chen, P L.]] | ||
[[Category: Jeffrey, P | [[Category: Jeffrey, P D.]] | ||
[[Category: Kinnucan, E.]] | [[Category: Kinnucan, E.]] | ||
[[Category: Lee, W | [[Category: Lee, W H.]] | ||
[[Category: Miller, J.]] | [[Category: Miller, J.]] | ||
[[Category: Pavletich, N | [[Category: Pavletich, N P.]] | ||
[[Category: Sun, Y.]] | [[Category: Sun, Y.]] | ||
[[Category: Thoma, N | [[Category: Thoma, N H.]] | ||
[[Category: Yang, H.]] | [[Category: Yang, H.]] | ||
[[Category: Zheng, N.]] | [[Category: Zheng, N.]] | ||
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[[Category: tumor suppressor]] | [[Category: tumor suppressor]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:55:36 2008'' | ||
Revision as of 11:55, 21 February 2008
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Structure of a BRCA2-DSS1 complex
Overview
Mutations in the BRCA2 (breast cancer susceptibility gene 2) tumor suppressor lead to chromosomal instability due to defects in the repair of double-strand DNA breaks (DSBs) by homologous recombination, but BRCA2's role in this process has been unclear. Here, we present the 3.1 angstrom crystal structure of a approximately 90-kilodalton BRCA2 domain bound to DSS1, which reveals three oligonucleotide-binding (OB) folds and a helix-turn-helix (HTH) motif. We also (i) demonstrate that this BRCA2 domain binds single-stranded DNA, (ii) present its 3.5 angstrom structure bound to oligo(dT)9, (iii) provide data that implicate the HTH motif in dsDNA binding, and (iv) show that BRCA2 stimulates RAD51-mediated recombination in vitro. These findings establish that BRCA2 functions directly in homologous recombination and provide a structural and biochemical basis for understanding the loss of recombination-mediated DSB repair in BRCA2-associated cancers.
Disease
Known disease associated with this structure: Split hand/foot malformation, type 1 OMIM:[183600]
About this Structure
1MIU is a Protein complex structure of sequences from Homo sapiens and Mus musculus with HG as ligand. Full crystallographic information is available from OCA.
Reference
BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure., Yang H, Jeffrey PD, Miller J, Kinnucan E, Sun Y, Thoma NH, Zheng N, Chen PL, Lee WH, Pavletich NP, Science. 2002 Sep 13;297(5588):1837-48. PMID:12228710
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