DNA lesions and repair

Pfeiffer, Petra; Göttlich, Bernd; Reichenberger, Susanne; Feldmann, Elke; Daza, Paula; Ward, John F.; Milligan, Jamie R.; Mullenders, Leon H.F.; Natarajan, A.T.

doi:10.1016/s0165-1110(96)90029-9

Cited by 27 publications

(16 citation statements)

References 36 publications

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“…A very efficient repair of bleomycin-or X-ray-induced DNA breaks was previously reported for V. faba [23,24] as well as for mammalian cells (for review see [25]). Bleomycin-induced DNA damage appears to be repaired mainly by rapid end joining in both plants and in mammals [26,27], while repair of alkylation damage depends on other mechanisms of DNA repair.…”

Section: The Radiomimetic Bleomycinmentioning

confidence: 99%

DNA damage and repair in Arabidopsis thaliana as measured by the comet assay after treatment with different classes of genotoxins

Menke

Chen

Angelis

et al. 2001

Mutation Research/Genetic Toxicology and Environmental Mutagene

143

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The three protocols of the comet assay A/N, A/A and N/N were for the first time applied to the plant species Arabidopsis thaliana. The purpose of the experiments was to establish conditions for genotoxic exposure causing DNA damage in Arabidopsis nuclei. This is required for comprehensive gene expression profiling with the intention to screen for genes involved in response of Arabidopsis cells to genotoxic stress.Five chemicals belonging to different classes of mutagens (the monofunctional alkylating agents N-methyl-N-nitrosourea and methyl methanesulfonate, the polyfunctional alkylating agent mitomycin C, the radiomimetic bleomycin and the herbicide maleic hydrazide) were tested. Except for maleic hydrazide, dose-dependent increases in DNA damage were found using the A/N comet assay protocol. While a rapid repair of bleomycin-mediated SSBs and DSBs was found, no significant reduction of DNA migration was observed up to 48 h after treatment with the monofunctional alkylating agents.

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Section: The Radiomimetic Bleomycinmentioning

confidence: 99%

DNA damage and repair in Arabidopsis thaliana as measured by the comet assay after treatment with different classes of genotoxins

Menke

Chen

Angelis

et al. 2001

Mutation Research/Genetic Toxicology and Environmental Mutagene

143

View full text Add to dashboard Cite

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“…Both IR and UV cause DNA lesions, IR primarily causing DNA strand breaks, whereas UV light predominantly induces pyrimidine dimers and 6-4 photoproducts (Pfeiffer et al, 1996). IR and UV treatment also trigger the generation of reactive oxygen species (ROS), which can cause lipid peroxidation, glutathione depletion and oxidation of proteins (Mercurio and Manning, 1999).…”

Section: Introductionmentioning

confidence: 99%

Induction of ATF3 by ionizing radiation is mediated via a signaling pathway that includes ATM, Nibrin1, stress-induced MAPkinases and ATF-2

et al. 2003

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“…There is evidence that most common chromosome aberrations observed in cells exposed to IR derive either from unrepaired or misrepaired DSBs (Bryant, 1984(Bryant, , 1988Natarajan, 2002;Natarajan et al, 1986;Obe et al, 2002;Pfeiffer et al, 1996). It is likely that pathway selection for the removal of these lesions from the genome will also determine the probability that a particular DSB will remain unrepaired, or how it will be misrepaired to a chromosomal aberration.…”

mentioning

confidence: 99%

Mechanisms of DNA double strand break repair and chromosome aberration formation

Iliakis

Wang

Perrault

et al. 2004

Cytogenet Genome Res

364

258

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It is widely accepted that unrepaired or misrepaired DNA double strand breaks (DSBs) lead to the formation of chromosome aberrations. DSBs induced in the DNA of higher eukaryotes by endogenous processes or exogenous agents can in principle be repaired either by non-homologous endjoining (NHEJ), or homology directed repair (HDR). The basis on which the selection of the DSB repair pathway is made remains unknown but may depend on the inducing agent, or process. Evaluation of the relative contribution of NHEJ and HDR specifically to the repair of ionizing radiation (IR) induced DSBs is important for our understanding of the mechanisms leading to chromosome aberration formation. Here, we review recent work from our laboratories contributing to this line of inquiry. Analysis of DSB rejoining in irradiated cells using pulsed-field gel electrophoresis reveals a fast component operating with half times of 10–30 min. This component of DSB rejoining is severely compromised in cells with mutations in DNA-PKcs, Ku, DNA ligase IV, or XRCC4, as well as after chemical inhibition of DNA-PK, indicating that it reflects classical NHEJ; we termed this form of DSB rejoining D-NHEJ to signify its dependence on DNA-PK. Although chemical inhibition, or mutation, in any of these factors delays processing, cells ultimately remove the majority of DSBs using an alternative pathway operating with slower kinetics (half time 2–10 h). This alternative, slow pathway of DSB rejoining remains unaffected in mutants deficient in several genes of the RAD52 epistasis group, suggesting that it may not reflect HDR. We proposed that it reflects an alternative form of NHEJ that operates as a backup (B-NHEJ) to the DNA-PK-dependent (D-NHEJ) pathway. Biochemical studies confirm the presence in cell extracts of DNA end joining activities operating in the absence of DNA-PK and indicate the dominant role for D-NHEJ, when active. These observations in aggregate suggest that NHEJ, operating via two complementary pathways, B-NHEJ and D-NHEJ, is the main mechanism through which IR-induced DSBs are removed from the DNA of higher eukaryotes. HDR is considered to either act on a small fraction of IR induced DSBs, or to engage in the repair process at a step after the initial end joining. We propose that high speed D-NHEJ is an evolutionary development in higher eukaryotes orchestrated around the newly evolved DNA-PKcs and pre-existing factors. It achieves within a few minutes restoration of chromosome integrity through an optimized synapsis mechanism operating by a sequence of protein-protein interactions in the context of chromatin and the nuclear matrix. As a consequence D-NHEJ mostly joins the correct DNA ends and suppresses the formation of chromosome aberrations, albeit, without ensuring restoration of DNA sequence around the break. B-NHEJ is likely to be an evolutionarily older pathway with less optimized synapsis mechanisms that rejoins DNA ends with kinetics of several hours. The slow kinetics and suboptimal synapsis mechanisms of B-NHEJ allow more time for ...

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DNA lesions and repair

Cited by 27 publications

References 36 publications

DNA damage and repair in Arabidopsis thaliana as measured by the comet assay after treatment with different classes of genotoxins

DNA damage and repair in Arabidopsis thaliana as measured by the comet assay after treatment with different classes of genotoxins

Induction of ATF3 by ionizing radiation is mediated via a signaling pathway that includes ATM, Nibrin1, stress-induced MAPkinases and ATF-2

Mechanisms of DNA double strand break repair and chromosome aberration formation

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