1mje: Difference between revisions
New page: left|200px<br /> <applet load="1mje" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mje, resolution 3.5Å" /> '''STRUCTURE OF A BRCA2... |
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[[Image:1mje.gif|left|200px]]<br /> | [[Image:1mje.gif|left|200px]]<br /><applet load="1mje" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1mje, resolution 3.5Å" /> | caption="1mje, resolution 3.5Å" /> | ||
'''STRUCTURE OF A BRCA2-DSS1-SSDNA COMPLEX'''<br /> | '''STRUCTURE OF A BRCA2-DSS1-SSDNA 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== | ||
1MJE 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]. Full crystallographic information is available from [http:// | 1MJE 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]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MJE 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 13:55:43 2008'' | ||
Revision as of 11:55, 21 February 2008
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STRUCTURE OF A BRCA2-DSS1-SSDNA 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
1MJE is a Protein complex structure of sequences from Homo sapiens and Mus musculus. 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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