View source for 2pie

[[Image:2pie.jpg|left|200px]]

 {{Structure
|PDB= 2pie |SIZE=350|CAPTION= <scene name='initialview01'>2pie</scene>, resolution 1.350&Aring;
|SITE= 
|LIGAND= <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>
|ACTIVITY= 
|GENE= RNF8, KIAA0646 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
|DOMAIN=
|RELATEDENTRY=[[2csw|2CSW]]
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pie OCA], [http://www.ebi.ac.uk/pdbsum/2pie PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2pie RCSB]</span>
}}

'''Crystal structure of the FHA domain of RNF8 in complex with its optimal phosphopeptide'''


==Overview==
DNA-damage signaling utilizes a multitude of posttranslational modifiers as molecular switches to regulate cell-cycle checkpoints, DNA repair, cellular senescence, and apoptosis. Here we show that RNF8, a FHA/RING domain-containing protein, plays a critical role in the early DNA-damage response. We have solved the X-ray crystal structure of the FHA domain structure at 1.35 A. We have shown that RNF8 facilitates the accumulation of checkpoint mediator proteins BRCA1 and 53BP1 to the damaged chromatin, on one hand through the phospho-dependent FHA domain-mediated binding of RNF8 to MDC1, on the other hand via its role in ubiquitylating H2AX and possibly other substrates at damage sites. Moreover, RNF8-depleted cells displayed a defective G2/M checkpoint and increased IR sensitivity. Together, our study implicates RNF8 as a novel DNA-damage-responsive protein that integrates protein phosphorylation and ubiquitylation signaling and plays a critical role in the cellular response to genotoxic stress.

==About this Structure==
2PIE is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PIE OCA]. 

==Reference==
RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly., Huen MS, Grant R, Manke I, Minn K, Yu X, Yaffe MB, Chen J, Cell. 2007 Nov 30;131(5):901-14. Epub 2007 Nov 20. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18001825 18001825]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Grant, R A.]]
[[Category: Yaffe, M B.]]
[[Category: complex]]
[[Category: fha domain]]
[[Category: ligase]]
[[Category: phosphopeptide]]
[[Category: signaling protein]]

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