Journal ArticleDOI
DNA damage foci: Meaning and significance
Kai Rothkamm,Stephen Barnard,Jayne Moquet,Michele Ellender,Zohaib Rana,Susanne Burdak-Rothkamm +5 more
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TLDR
The biological meaning and significance of DNA damage foci is reviewed, looking specifically at a range of different settings in which such markers of DNAdamage and repair are being studied and interpreted.Abstract:
The discovery of DNA damage response proteins such as γH2AX, ATM, 53BP1, RAD51, and the MRE11/RAD50/NBS1 complex, that accumulate and/or are modified in the vicinity of a chromosomal DNA double-strand break to form microscopically visible, subnuclear foci, has revolutionized the detection of these lesions and has enabled studies of the cellular machinery that contributes to their repair. Double-strand breaks are induced directly by a number of physical and chemical agents, including ionizing radiation and radiomimetic drugs, but can also arise as secondary lesions during replication and DNA repair following exposure to a wide range of genotoxins. Here we aim to review the biological meaning and significance of DNA damage foci, looking specifically at a range of different settings in which such markers of DNA damage and repair are being studied and interpreted.read more
Citations
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Journal ArticleDOI
DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer.
Ruixue Huang,Ping-Kun Zhou +1 more
TL;DR: An update on the novel and promising druggable targets emerging from DDR pathways that can be exploited for radiosensitization is provided and challenges for ionizing radiation-induced signal transduction and targeted therapy are discussed.
Journal ArticleDOI
The Role of SIRT1 on DNA Damage Response and Epigenetic Alterations in Cancer
TL;DR: The recent findings on the interplay among SIRT1, oxidative stress, and DNA repair machinery and its impact on normal and cancer cells are discussed.
Journal ArticleDOI
Do DNA Double-Strand Breaks Drive Aging?
Ryan R. White,Jan Vijg +1 more
TL;DR: The possibility that D SBs are major drivers of intrinsic aging is discussed, highlighting the dynamics of spontaneous DSBs in relation to aging, the distinct age-related pathologies induced by DSBS, and the segmental progeroid phenotypes in humans and mice with genetic defects in DSB repair.
Journal ArticleDOI
Initiator-Loaded Gold Nanocages as a Light-Induced Free-Radical Generator for Cancer Therapy
TL;DR: A new therapeutic strategy based on the light-induced generation of free radicals for cancer therapy is reported, using Initiator-loaded gold nanocages (AuNCs) as the free-radical generator.
Journal ArticleDOI
Exosomes Serve as Nanoparticles to Deliver Anti-miR-214 to Reverse Chemoresistance to Cisplatin in Gastric Cancer
Xinyi Wang,Haiyang Zhang,Ming Bai,Tao Ning,Shaohua Ge,Ting Deng,Rui Liu,Le Zhang,Guoguang Ying,Yi Ba +9 more
TL;DR: Caudally injected exo-anti-214 was applied to reverse chemoresistance and repress tumor growth in vivo due to the downregulation of miR-214 and overexpression of possible target proteins in tumors.
References
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Journal ArticleDOI
The DNA Damage Response: Making It Safe to Play with Knives
TL;DR: This review will focus on how the DDR controls DNA repair and the phenotypic consequences of defects in these critical regulatory functions in mammals.
Journal ArticleDOI
Megabase chromatin domains involved in DNA double-strand breaks in vivo.
TL;DR: The results offer direct visual confirmation that γ-H2AX forms en masse at chromosomal sites of DNA double-strand breaks and suggest the possible existence of units of higher order chromatin structure involved in monitoring DNA integrity.
Journal ArticleDOI
Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions
Vassilis G. Gorgoulis,Leandros-Vassilios F. Vassiliou,Panagiotis Karakaidos,Panayotis Zacharatos,Athanassios Kotsinas,Triantafillos Liloglou,Monica Venere,Richard A. DiTullio,Nikolaos G. Kastrinakis,Brynn Levy,Dimitris Kletsas,Akihiro Yoneta,Meenhard Herlyn,Christos Kittas,Thanos D. Halazonetis,Thanos D. Halazonetis +15 more
TL;DR: A panel of human lung hyperplasias, all of which retained wild-type p53 genes and had no signs of gross chromosomal instability, and found signs of a DNA damage response, including histone H2AX and Chk2 phosphorylation, p53 accumulation, focal staining of p53 binding protein 1 (53BP1) and apoptosis as discussed by the authors.
Activation of the DNA damage checkpointandgenomicinstabilityin human precancerous lesions
Vassilis G. Gorgoulis,Leandros-Vassilios F. Vassiliou,Panagiotis Karakaidos,Panayotis Zacharatos,Athanassios Kotsinas,Triantafillos Liloglou,Monica Venere,Richard A. DiTullio,Meenhard Herlyn,Christos Kittas,Thanos D. Halazonetis,Roy Castle +11 more
TL;DR: It is proposed that, from its earliest stages, cancer development is associated with DNA replication stress, which leads to DNA double-strand breaks, genomic instability and selective pressure for p53 mutations.
Journal ArticleDOI
Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses
Kai Rothkamm,Markus Löbrich +1 more
TL;DR: Evidence is presented that foci of γ-H2AX (a phosphorylated histone), detected by immunofluorescence, are quantitatively the same as DSBs and are capable of quantifying the repair of individual D SBs, allowing the investigation of DSB repair after radiation doses as low as 1 mGy, an improvement by several orders of magnitude over current methods.
Related Papers (5)
Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses
Kai Rothkamm,Markus Löbrich +1 more