Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins.

Cell | Nov 30, 2007

Accumulation of repair proteins on damaged chromosomes is required to restore genomic integrity. However, the mechanisms of protein retention at the most destructive chromosomal lesions, the DNA double-strand breaks (DSBs), are poorly understood. We show that RNF8, a RING-finger ubiquitin ligase, rapidly assembles at DSBs via interaction of its FHA domain with the phosphorylated adaptor protein MDC1. This is accompanied by an increase in DSB-associated ubiquitylations and followed by accumulation of 53BP1 and BRCA1 repair proteins. Knockdown of RNF8 or disruption of its FHA or RING domains impaired DSB-associated ubiquitylation and inhibited retention of 53BP1 and BRCA1 at the DSB sites. In addition, we show that RNF8 can ubiquitylate histone H2A and H2AX, and that its depletion sensitizes cells to ionizing radiation. These data suggest that MDC1-mediated and RNF8-executed histone ubiquitylation protects genome integrity by licensing the DSB-flanking chromatin to concentrate repair factors near the DNA lesions.

Pubmed ID: 18001824 RIS Download

Mesh terms: BRCA1 Protein | Binding Sites | Cell Survival | Chromatin | DNA Breaks, Double-Stranded | DNA Repair Enzymes | DNA-Binding Proteins | Histones | Humans | Intracellular Signaling Peptides and Proteins | Models, Biological | Nuclear Proteins | Phosphorylation | Protein Binding | Protein Structure, Tertiary | Trans-Activators | Tumor Cells, Cultured | Tumor Suppressor p53-Binding Protein 1 | Ubiquitination

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.