Cited by 338DNA Repair MechanismsEffects of Radiation ExposureGenomics and Chromatin Dynamics

Assembly and function of DNA double-strand break repair foci in mammalian cells

Bekker-Jensen, Simon, Mailand, Niels·2010·DNA Repair

Abstract

DNA double-strand breaks (DSBs) are among the most cytotoxic types of DNA damage, which if left unrepaired can lead to mutations or gross chromosomal aberrations, and promote the onset of diseases associated with genomic instability such as cancer. One of the most discernible hallmarks of the cellular response to DSBs is the accumulation and local concentration of a plethora of DNA damage signaling and repair proteins in the vicinity of the lesion, initiated by ATM-mediated phosphorylation of H2AX (γ-H2AX) and culminating in the generation of distinct nuclear compartments, so-called Ionizing Radiation-Induced Foci (IRIF). The assembly of proteins at the DSB-flanking chromatin occurs in a highly ordered and strictly hierarchical fashion. To a large extent, this is achieved by regulation of protein-protein interactions triggered by a variety of post-translational modifications including phosphorylation, ubiquitylation, SUMOylation, and acetylation. Over the last decade, insight into the identity of proteins residing in IRIF and the molecular underpinnings of their retention at these structures has been vastly expanded. Despite such advances, however, our understanding of the biological relevance of such DNA repair foci still remains limited. In this review, we focus on recent discoveries on the mechanisms that govern the formation of IRIF, and discuss the implications of such findings in light of our understanding of the physiological importance of these structures.

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Crossref · 10.1016/j.dnarep.2010.09.010

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  • The MRN complex senses and processes double-strand DNA breaks and activates downstream DNA damage response proteins such as ATM.

    “The MRN complex is important in sensing and processing double-strand DNA breaks, as well as activating downstream DNA damage response proteins that mediate or signal for DNA repair, such as the DNA damage-induced kinase ATM.9–13”
  • Full activation of ATM after DNA double-strand breaks requires Nbs1 of the MRN complex.

    “Full activation of ATM following DNA double-strand breaks requires Nbs1 of the MRN complex.9,11–13”
  • Phosphorylation of H2AX and S/T-Q sites occurs rapidly after DNA breaks.

    “Phosphorylation of H2AX and S/T-Q sites, both of which are targets of ATM, occurs rapidly after DNA breaks.9,37,38”

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Authors
Bekker-Jensen, S., & Mailand, N.
Affiliations
University of Copenhagen (DK)
Corresponding author
Mailand, Niels
Venue
DNA Repair
Publisher
Elsevier BV
Published
2010-12
Volume
9
Issue
12
Pages
1219-1228
ISSN
  • 1568-7856 (ISSN-L)
  • 1568-7864
OpenAlex
W1999541392
Cited by
338
References
112
Citations by year
2026: 5 · 2025: 9 · 2024: 6 · 2023: 8 · 2022: 11 · 2021: 17 · 2020: 16 · 2019: 14 · 2018: 16 · 2017: 24 · 2016: 21 · 2015: 33 · 2014: 45 · 2013: 36 · 2012: 45
FWCI
3.17
Type
journal article
Language
en
Open access
closed
Locations
  • DNA repair (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
  • Lundbeckfonden
  • Novo Nordisk Fonden
  • Kræftens Bekæmpelse
  • Sundhed og Sygdom, Det Frie Forskningsråd
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
DNA double-strand break repair, ionizing radiation-induced foci, DNA damage signaling, γH2AX, protein-protein interaction, post-translational modification, ubiquitination, SUMOylation, acetylation, chromatin assembly, genomic instability, mammalian cells
MeSH terms
Tumor Suppressor p53-Binding Protein 1, Animals, Cell Nucleus, Chromatin, DNA Repair, DNA-Binding Proteins, Histones, Humans, Nuclear Proteins, Phosphorylation, Protein Processing, Post-Translational, Trans-Activators, Cell Cycle Proteins, BRCA1 Protein, Guanine Nucleotide Exchange Factors, Genomic Instability, Ubiquitin-Protein Ligases, Multiprotein Complexes, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, DNA Breaks, Double-Stranded, Ubiquitination

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