The ubiquitin-selective segregase VCP/p97 orchestrates the response to DNA double-strand breaks

@article{Meerang2011TheUS,
  title={The ubiquitin-selective segregase VCP/p97 orchestrates the response to DNA double-strand breaks},
  author={Mayura Meerang and Danilo Ritz and Shreya Paliwal and Zuzana Garajov{\`a} and Matthias Bosshard and Niels Mailand and Pavel Janscak and Ulrich Hübscher and Hemmo Meyer and Kristijan Ramadan},
  journal={Nature Cell Biology},
  year={2011},
  volume={13},
  pages={1376-1382}
}
Unrepaired DNA double-strand breaks (DSBs) cause genetic instability that leads to malignant transformation or cell death. Cells respond to DSBs with the ordered recruitment of signalling and repair proteins to the site of lesion. Protein modification with ubiquitin is crucial for the signalling cascade, but how ubiquitylation coordinates the dynamic assembly of these complexes is poorly understood. Here, we show that the human ubiquitin-selective protein segregase p97 (also known as VCP… 
The role of ubiquitin-dependent segregase p97 (VCP or Cdc48) in chromatin dynamics after DNA double strand breaks
DNA double strand breaks (DSBs) are the most cytotoxic DNA lesions and, if not repaired, lead to chromosomal rearrangement, genomic instability and cell death. Cells have evolved a complex network of
The p97–Ataxin 3 complex regulates homeostasis of the DNA damage response E3 ubiquitin ligase RNF8
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It is proposed that the p97–ATX3 complex is the essential machinery for regulation of RNF8 homeostasis under both physiological and genotoxic conditions and that targeting ATX3 may be a promising strategy to radio‐sensitise BRCA‐deficient cancers.
The proteasomal de‐ubiquitinating enzyme POH1 promotes the double‐strand DNA break response
TLDR
It is demonstrated that proteasomal POH1 is a key de‐ubiquitinating enzyme that regulates ubiquitin conjugates generated in response to damage and that several aspects of the DSB response are regulated by the proteasome.
RNF8 ubiquitinates RecQL4 and promotes its dissociation from DNA double strand breaks
TLDR
It is demonstrated that the ubiquitination event mediated by RNF8 constitutes an essential component for RecQL4’s function in DSB repair.
E4 ligase–specific ubiquitination hubs coordinate DNA double-strand-break repair and apoptosis
TLDR
The E4 ubiquitin ligase UFD-2 is identified as a mediator of DNA-damage-induced apoptosis in a genetic screen in Caenorhabditis elegans and a central role is established in the coordination between the DNA-repair process and the apoptotic response.
VCP/p97 Extracts Sterically Trapped Ku70/80 Rings from DNA in Double-Strand Break Repair.
TLDR
By means of reconstitution of DSB repair on beads, it is demonstrated here that DNA-locked Ku rings are released by the AAA-ATPase p97, illustrating the ability of p97 to segregate even tightly bound protein complexes for release from DNA.
Ring Finger Protein RNF169 Antagonizes the Ubiquitin-dependent Signaling Cascade at Sites of DNA Damage*
TLDR
This study unveils RNF169 as a component in DNA damage signal transduction and adds to the complexity of regulatory ubiquitylation in genome stability maintenance.
INT6/EIF3E Controls the RNF8-Dependent Ubiquitylation Pathway and Facilitates DNA Double-Strand Break Repair in Human Cells.
TLDR
The antioncogenic breast cancer factor INT6/EIF3E is identified as an essential regulator of DSB repair that promotes homologous recombination (HR)-mediated repair and, to a lesser extent, nonhomologous end-joining repair.
RYBP Is a K63-Ubiquitin-Chain-Binding Protein that Inhibits Homologous Recombination Repair.
Ring1-YY1-binding protein (RYBP) is a member of the non-canonical polycomb repressive complex 1 (PRC1), and like other PRC1 members, it is best described as a transcriptional regulator. However,
DVC1 (C1orf124) recruits the p97 protein segregase to sites of DNA damage
TLDR
It is shown that DVC1 recruits p97 to sites of DNA damage, where it is proposed that p97 facilitates the extraction of the translesion synthesis (TLS) polymerase (Pol) η during DNA repair to prevent excessive TLS and limit the incidence of mutations induced by DNA damage.
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