2pie
From Proteopedia
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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 Homo sapiens. Full crystallographic information is available from 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:18001825
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