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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
44
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pubmed:dateCreated |
2008-10-28
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pubmed:abstractText |
The BARD1 N-terminal RING domain binds BRCA1 while the BARD1 C-terminal ankyrin and tandem BRCT repeat domains bind CstF-50 to modulate mRNA processing and RNAP II stability in response to DNA damage. Here we characterize the BARD1 structural biochemistry responsible for CstF-50 binding. The crystal structure of the BARD1 BRCT domain uncovers a degenerate phosphopeptide binding pocket lacking the key arginine required for phosphopeptide interactions in other BRCT proteins. Small angle X-ray scattering together with limited proteolysis results indicates that ankyrin and BRCT domains are linked by a flexible tether and do not adopt a fixed orientation relative to one another. Protein pull-down experiments utilizing a series of purified BARD1 deletion mutants indicate that interactions between the CstF-50 WD-40 domain and BARD1 involve the ankyrin-BRCT linker but do not require ankyrin or BRCT domains. The structural plasticity imparted by the ANK-BRCT linker helps to explain the regulated assembly of different protein BARD1 complexes with distinct functions in DNA damage signaling including BARD1-dependent induction of apoptosis plus p53 stabilization and interactions. BARD1 architecture and plasticity imparted by the ANK-BRCT linker are suitable to allow the BARD1 C-terminus to act as a hub with multiple binding sites to integrate diverse DNA damage signals directly to RNA polymerase.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-10196224,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-10354416,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-10431175,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-10468571,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-10477523,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-10669729,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-11134934,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-11257228,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-11301010,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-11371467,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-11459828,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-11573085,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-11573086,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-11779501,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-11807980,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-11943588,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-12176841,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-12427738,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-12461176,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-12732733,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-12941707,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-14576432,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-14576433,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-14578343,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-15125843,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-15133502,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-15133503,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-15152081,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-15159397,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-15280660,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-15299926,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-15501676,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-15572765,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-15782130,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-15905410,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-16049003,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-16061562,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-16101277,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-16377563,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-16651405,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-17052461,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-17174478,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-17182256,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-17411046,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-17525342,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-17531814,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-17550235,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-17643121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-17643122,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-17848578,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-18078545,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-18164031,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-8521505,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-8898209,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-8944023,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-9000507,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-9002523,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-9034168,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-9425226,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-9738006,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18842000-9757107
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1520-4995
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
4
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pubmed:volume |
47
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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