Ubiquitination — An Evolving Role in DNA Repair

Upon DNA damage due to endogenous or exogenous causes, chromatin is dynamically modified, especially through posttranslational modifications (PTMs) of histones together with noncoding RNA expression. Both procedures modify accessibility of genes and regulatory genomic loci by protein factors and enzymes involved in gene expression as well as DNA repair processes. In addition, PTMs of proteins involved in genome integrity seem to play important roles in regulating their functions and protein–protein interactions (PPI). The most studied PTMs involved in DNA repair machinery function are histone phosphorylations, methylations/demethylations and to a lesser extent acetylations, allowing/prohibiting acces‐ sibility to double-strand break recognition and binding of factors/enzymes. Protein ubiquiti‐ nation – the covalent link of the small protein ubiquitin (Ub) to lysine residues of a target protein – was classically related to protein degradation, ensuring structural integrity control and/or protein turnover rate. This procedure involves the addition of multiple ubiquitin molecules in a specific manner, which targets the polyubiquitinated protein to the proteasome for degradation. In recent years, accumulating data unveiled a role for nondegrading ubiqui‐ tination of proteins involved in DNA repair pathways and cell fate decisions [1,2]. A welldocumented overview depicting the exceptional importance of ubiquitination in the restoration of genotoxic insults was carried out by a number of reviews, clearly pointing out ubiquitination and DNA damage response/repair interrelation [3]. The issue comprehensively covers practically all principal aspects of Ub function in the field. Therefore, many issues of the ubiquitin landscape at DNA double-strand breaks (DSBs) have been highlighted. As described, many challenges and puzzles remain to be solved regarding the intimate relation‐ ship between the DNA repair machinery and nondegrading ubiquitin signaling at DNA DSBs and the surrounding chromatin (Fig. 1) [3].

• Publication year

  2015

• Venue

  Unknown venue

• Publication date

  2015-11-18

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.5772/61582
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• Cullin Family Proteins and Tumorigenesis: Genetic Association and Molecular Mechanisms

  2015cited by this paper
• Regulation of Hedgehog signaling by ubiquitination

  2015cited by this paper
• Ubiquitin regulates dissociation of DNA repair factors from chromatin

  2015cited by this paper
• BRCA1, a ‘complex’ protein involved in the maintenance of genomic stability

  2015cited by this paper
• Reshaping chromatin after DNA damage: the choreography of histone proteins

  2014cited by this paper
• Chromatin modifications and DNA repair: beyond double-strand breaks

  2014cited by this paper
• DNA double-strand break repair pathway choice and cancer.

  2014influential reference
• RPA-coated single-stranded DNA as a platform for post-translational modifications in the DNA damage response

  2014cited by this paper
• DNA damage-specific deubiquitination regulates Rad18 functions to suppress mutagenesis

  2014cited by this paper
• A small ubiquitin binding domain inhibits ubiquitin-dependent protein recruitment to DNA repair foci

  2013cited by this paper
• Single-molecule sorting reveals how ubiquitylation affects substrate recognition and activities of FBH1 helicase

  2013cited by this paper
• Regulation of DNA damage responses by ubiquitin and SUMO.

  2013cited by this paper
• The ubiquitin specific protease USP34 promotes ubiquitin signaling at DNA double-strand breaks

  2013cited by this paper
• The chromatin response to DNA breaks: leaving a mark on genome integrity.

  2013cited by this paper
• A heat-stable polypeptide component of an ATP-dependent proteolytic system from reticulocytes. 1978.

  2012cited by this paper
• The ubiquitin code.

  2012cited by this paper
• Histone Ubiquitination and Deubiquitination in Transcription, DNA Damage Response, and Cancer

  2012cited by this paper
• Chfr and RNF8 synergistically regulate ATM activation

  2011cited by this paper
• Ub‐family modifications at the replication fork: Regulating PCNA‐interacting components

  2011cited by this paper
• RNF20–RNF40: A ubiquitin‐driven link between gene expression and the DNA damage response

  2011cited by this paper
• Ubiquitin ligase UBR3 regulates cellular levels of the essential DNA repair protein APE1 and is required for genome stability

  2011cited by this paper
• BMI1 Is Recruited to DNA Breaks and Contributes to DNA Damage-Induced H2A Ubiquitination and Repair

  2011cited by this paper
• Readers of histone modifications

  2011cited by this paper
• Requirement of ATM-dependent monoubiquitylation of histone H2B for timely repair of DNA double-strand breaks.

  2011cited by this paper
• Histone tails: Directing the chromatin response to DNA damage

  2011cited by this paper
• Ubiquitin‐family modifications in the replication of DNA damage

  2011cited by this paper
• DNA Repair - On the Pathways to Fixing DNA Damage and Errors

  2011cited by this paper
• Monoubiquitination of H2AX Protein Regulates DNA Damage Response Signaling

  2011cited by this paper
• Structure, assembly and homeostatic regulation of the 26S proteasome.

  2010cited by this paper
• The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks

  2009cited by this paper
• Principles of ubiquitin and SUMO modifications in DNA repair

  2009cited by this paper
• Nucleotide excision repair–induced H2A ubiquitination is dependent on MDC1 and RNF8 and reveals a universal DNA damage response

  2009cited by this paper
• The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage.

  2009influential reference
• Building ubiquitin chains: E2 enzymes at work

  2009cited by this paper
• The ubiquitin landscape at DNA double-strand breaks

  2009cited by this paper
• Histone Ubiquitination Associates with BRCA1-Dependent DNA Damage Response

  2008cited by this paper
• RAP80 Targets BRCA1 to Specific Ubiquitin Structures at DNA Damage Sites

  2007influential reference
• Ubiquitin-Binding Protein RAP80 Mediates BRCA1-Dependent DNA Damage Response

  2007influential reference
• Proteasome-Independent Functions of Ubiquitin in Endocytosis and Signaling

  2007cited by this paper
• Regulation of receptors and transporters by ubiquitination: new insights into surprisingly similar mechanisms.

  2007cited by this paper
• RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins.

  2007influential reference
• Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage

  2007influential reference
• RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly.

  2007influential reference
• Orchestration of the DNA-Damage Response by the RNF8 Ubiquitin Ligase

  2007cited by this paper
• Abraxas and RAP80 Form a BRCA1 Protein Complex Required for the DNA Damage Response

  2007influential reference
• DNA damage triggers nucleotide excision repair-dependent monoubiquitylation of histone H2A.

  2006cited by this paper
• Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage

  2005cited by this paper
• Ubiquitin: structures, functions, mechanisms.

  2004cited by this paper
• Non-traditional Functions of Ubiquitin and Ubiquitin-binding Proteins*

  2003cited by this paper
• NFBD1/MDC1 regulates ionizing radiation‐induced focus formation by DNA checkpoint signaling and repair factors

  2003cited by this paper
• MDC1 is a mediator of the mammalian DNA damage checkpoint

  2003cited by this paper
• The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction.

  2002cited by this paper
• Genome maintenance mechanisms for preventing cancer

  2001cited by this paper
• A heat-stable polypeptide component of an ATP-dependent proteolytic system from reticulocytes.

  1978cited by this paper

• No citing papers are available for this paper.