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2azm

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[[Image:2azm.gif|left|200px]]
[[Image:2azm.gif|left|200px]]
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{{Structure
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|PDB= 2azm |SIZE=350|CAPTION= <scene name='initialview01'>2azm</scene>, resolution 2.41&Aring;
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The line below this paragraph, containing "STRUCTURE_2azm", creates the "Structure Box" on the page.
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|SITE=
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|LIGAND= <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>
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|GENE= MDC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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|DOMAIN=
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{{STRUCTURE_2azm| PDB=2azm | SCENE= }}
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2azm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2azm OCA], [http://www.ebi.ac.uk/pdbsum/2azm PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2azm RCSB]</span>
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'''Crystal structure of the MDC1 brct repeat in complex with the histone tail of gamma-H2AX'''
'''Crystal structure of the MDC1 brct repeat in complex with the histone tail of gamma-H2AX'''
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[[Category: Stucki, M.]]
[[Category: Stucki, M.]]
[[Category: Yaffe, M B.]]
[[Category: Yaffe, M B.]]
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[[Category: brct repeat]]
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[[Category: Brct repeat]]
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[[Category: dna damage]]
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[[Category: Dna damage]]
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[[Category: protein-phosphopeptide complex]]
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[[Category: Protein-phosphopeptide complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:39:55 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:59:27 2008''
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Revision as of 16:39, 3 May 2008

Template:STRUCTURE 2azm

Crystal structure of the MDC1 brct repeat in complex with the histone tail of gamma-H2AX


Overview

Histone variant H2AX phosphorylation in response to DNA damage is the major signal for recruitment of DNA-damage-response proteins to regions of damaged chromatin. Loss of H2AX causes radiosensitivity, genome instability, and DNA double-strand-break repair defects, yet the mechanisms underlying these phenotypes remain obscure. Here, we demonstrate that mammalian MDC1/NFBD1 directly binds to phospho-H2AX (gammaH2AX) by specifically interacting with the phosphoepitope at the gammaH2AX carboxyl terminus. Moreover, through a combination of biochemical, cell-biological, and X-ray crystallographic approaches, we reveal the molecular details of the MDC1/NFBD1-gammaH2AX complex. These data provide compelling evidence that the MDC1/NFBD1 BRCT repeat domain is the major mediator of gammaH2AX recognition following DNA damage. We further show that MDC1/NFBD1-gammaH2AX complex formation regulates H2AX phosphorylation and is required for normal radioresistance and efficient accumulation of DNA-damage-response proteins on damaged chromatin. Thus, binding of MDC1/NFBD1 to gammaH2AX plays a central role in the mammalian response to DNA damage.

About this Structure

2AZM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks., Stucki M, Clapperton JA, Mohammad D, Yaffe MB, Smerdon SJ, Jackson SP, Cell. 2005 Dec 29;123(7):1213-26. PMID:16377563 Page seeded by OCA on Sat May 3 19:39:55 2008

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