RNF8 Ubiquitylates Histones at DNA Double-Strand Breaks and Promotes Assembly of Repair Proteins

@article{Mailand2007RNF8UH,
  title={RNF8 Ubiquitylates Histones at DNA Double-Strand Breaks and Promotes Assembly of Repair Proteins},
  author={Niels Mailand and Simon Bekker-Jensen and Helene Faustrup and F. Melander and Jiri Bartek and Claudia Lukas and Jiri Lukas},
  journal={Cell},
  year={2007},
  volume={131},
  pages={887-900}
}
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… Expand

Paper Mentions

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Evidence is provided that, while RNF8 is necessary to trigger the DSB-associated ubiquitylation, it is not sufficient to sustain conjugated ubiquitin in this compartment, which defines a new pathway involving sequential ubiquitylations on damaged chromosomes and uncovers a functional cooperation between E3 ligases in genome maintenance. Expand
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TLDR
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TLDR
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TLDR
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RNF4, a SUMO-targeted ubiquitin E3 ligase, promotes DNA double-strand break repair.
TLDR
It is established that RNF4 regulates turnover of the DSB-responsive factors MDC1 and replication protein A at DNA damage sites and that R NF4-depleted cells fail to effectively replace RPA by the homologous recombination factors BRCA2 and RAD51 on resected DNA. Expand
Writers, Readers, and Erasers of Histone Ubiquitylation in DNA Double-Strand Break Repair
TLDR
This review provides a comprehensive account of how DSB-induced histone ubiquitylation is sensed, decoded and modulated by an elaborate array of repair factors and regulators for optimal protection of genome integrity, as well as cell and organismal fitness. Expand
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