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Results for “DNA strand breaks”

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At least 19 recordsLinked to original sources
PubMed1979

Qualitative and quantitative aspects of intercalator-induced DNA strand breaks.

The intercalating agents, adriamycin and ellipticine, were previously found to produce DNA strand breaks associated with DNA-protein crosslinks in mouse leukemia L1210 cells. The current work explores the nature of the agents that produce this effect and the quantitative relationship between the breaks and crosslinks. The protein-associated DNA breaks were produced by a wide variety of intercalators in addition to the above-mentioned compounds: actinomycin D, daunoycin, ethidium and lucanthone (miracil D). Treatment with several drugs that bind to DNA without intercalation, or that inhibit DNA synthesis without binding to DNA, did not cause DNA breaks. The strand break and crosslink frequencies were quantitated by means of alkaline elution methods. The strand break and crosslink frequencies were found to be within a factor of 2 of each other over a range of concentrations of adriamycin and ellipticine. It is proposed that intercalation-induced distortion of the DNA helix leads to strand scission by a nuclease which becomes bound to one terminus of the break so as to form a DNA-protein crosslink.

Alkaloids↗
PubMed1978

[Single-strand DNA breaks and chromosome aberrations in the hepatocytes of mice of different ages].

The same damages were found to occur in hepatocyte DNA from old mice of different strains by means of sedimentation in alkaline sucrose concentration gradient. At the same time, the number of hepatocytes with aberrant chromosomes is strongly different in these strains. From these data an assumption is made that some other damages being accumulated with aging are responsible for chromosome aberrations except for single-strand DNA breaks. The number of single-strand breaks registered in hepatocyte DNA of the old animals under gamma-irradiation is two-three times more than that of the young animals, though the rates of repair of the induced single-strand breaks in DNA are the same for mice of different age and strains.

Aging↗
PubMed2025

Arabidopsis thaliana FANCONI ANAEMIA I (FANCI) has roles in the repair of interstrand crosslinks and CRISPR-Cas9 induced DNA double strand breaks.

DNA repair is crucial for genome stability, in particular for plants which are exposed to high levels of damage arising from UV irradiation, soil pollutants and reactive oxygen species. Damage that affects both strands of the DNA duplex is harder to repair due to both the lack of a template strand and the potential for physical separation of fragmented chromosomes. As such, DNA double-strand breaks (DSBs) and interstrand DNA crosslinks (ICL) are particularly cytotoxic forms of damage. Here we report the functions of FANCONI ANAEMIA I (FANCI), an Arabidopsis thaliana homologue of the mammalian ICL repair protein. We show that in plant cells, as in mammals, FANCI forms a nuclear localised complex with FANCD2. Genetic analysis of plants lacking FANCI displays significant hypersensitivity to the DNA crosslinking reagent mitomycin C. Furthermore, mutation of FANCI in combination with mutations in a second ICL repair factor, METHYL METHANESULFONATE AND UV-SENSITIVE PROTEIN 81 (MUS81), results in increased levels of programmed cell death compared to the corresponding single mutants, revealing roles in maintaining plant genome stability. Sequence analysis of mutational repair of CRISPR-Cas9-induced DSBs revealed that FANCI promotes single nucleotide insertions and reduces longer deletions. This pattern of mutations may reflect roles for FA proteins in replication-coupled repair of a subset of DSBs. Taken together, this analysis finds evidence for multiple roles for FANCI in the maintenance of plant genome stability.

Arabidopsis↗
PubMed1977

Repair of single-strand DNA breaks and recovery of chromosomal and chromatid aberrations after treatment of plant seeds with propyl methanesulfonate in vivo.

Repair of single-strand breaks of DNA and simultaneous recovery of chromosomal aberrations were studied after treatment of barley seeds with the monofunctional alkylating chemical mutagen, propyl methanesulfonate in vivo. In soaked seeds the diminution of single-strand breaks of DNA induced by PMS was correlated with the decrease of chromosomal aberrations, whereas in dried seeds the repair of DNA breaks was depressed and, in accord with this, the frequency of chromosomal aberrations increased. The prolonged storage of seeds led to a more delayed repair of chromosomal aberrations in dry seeds and a more delayed accelerated repair in soaked seeds.

Chromatids↗
PubMed1977

[Mechanism of the formation of single-stranded DNA breaks under the effect of prednisolone on rat liver thymocytes].

Rat liver thymocytes were incubated in vitro with prednisolon, and molecular weight of single-stranded DNA was estimated in alkaline lysates of nuclei by viscosity methods. The number of single-stranded breaks was estimated, which originate in DNA after 3 hours of incubation with prednisolon at a concentration of 3-10(-9) M--3-10(-4) M. Maximal hormone effect was produced within 30 min., and it remained constant for the rest 3 hours of the incubation. Cycloheximide prevented hormone-induced DNA depolymerization, and actinomycin D only slightly inhibited the formation of single-stranded DNA breaks, originated after 30 min. incubation of thymocytes with prednisolon, were repaired after their washing and reincubation in the fresh medium for 1 hour at 37 degrees C. The washing of thymocytes and their reincubation for 3 hours resulted in the decrease of the molecular weight of single-stranded DNA. Possible mechanism of the formation of single-stranded DNA breaks in prednisolon-induced thymocytes is discussed.

Animals↗
PubMed1979

Radiation-induced DNA strand breaks and their repair in the developing rat brain.

Rats, 5, 10 or 25 days old, were 60 Co gamma irradiated. The induction of DNA strand breaks was studied after killing the rats within 1 min after irradiation, and the repair of the induced breaks after various intervals up to 180 min. Cell suspensions were prepared from the brain and samples were transferred into alkaline solutions. The fraction of DNA remaining double-stranded after 30 min alkali treatment was estimated after separation of single- and double-stranded DNA on hydroxylapatite. The amount of DNA strand breaks induced per Gray (1--8 Gray) was found to be in accordance with earlier in vivo studies of the mouse small intestine and mouse spleen. The DNA strand breaks in the rat brain induced by 4 Gray 60Co gamma irradiation were repaired 30 min after irradiation in all age groups studied.

Animals↗
PubMed1978

DNA strand breaks in resistant and sensitive murine lymphoma cells detected by the hydroxyapatite chromatographic technique.

Strand breaks were determined in L5178YS and L5178YR cell lines with DOS of 0.75 and 1.75 Gy, respectively, for 7 MeV electrons. The hydroxyapatite chromatographic technique was used to measure the breaks produced by 7 MeV electrons or 7 MeV neutrons immediately after irradiation or after maximal repair. Oxygen enhancement values for survival as well as strand breaks were determined for both cell lines and both qualities of radiation. The results indicate that despite a differential response to the lethal effects of radiation the levels of DNA strand breaks induced in these two lines were identical. Furthermore the values obtained for oxygen enhancement ratios (o.e.r.) and relative biological effectiveness (r.b.e.) for DNA strand breaks were different from those for cell survival. These results show that the difference in radiation sensitivity for cell killing is not reflected by the extent of DNA strand breaks measured by this method.

Animals↗
PubMed1979

Cytotoxicity of an 125I-labeled DNA-binding compound that induces double-stranded DNA breaks.

[125I]Iodorivanol (6,9-diamino-2-ethoxy-5-[125]iodoacridine) has been prepared by direct iodination of rivanol (6.9-diamino-2-ethoxyacridine). In vitro binding of [125I]iodorivanol to PM2 DNA resulted in induction of double-stranded DNA breaks following decay of the 125I atom, presumably in the same way as decay of 125I atoms in 125I-labeled DNA causes double-stranded DNA breaks. Treatment of mouse L-cell cultures with [125I]iodorivanol resulted in a cell kill, the extent of which was dependent on the 125I specific activity and the duration of exposure. A clonogenic assay was used to quantitate cell kill. It was concluded that at least some of the [125I]iodorivanol in the culture medium was taken up by the cells, transported to the nucleus, and bound to DNA and that subsequent decay of the 125I atoms induced double-stranded DNA breaks in the genome, with consequent loss of viability. 125I-labeled DNA-binding compounds are suggested as a novel class of cytotoxic agents.

Acridines↗
PubMed1975

Repair of DNA strand breaks in progeric fibroblasts and aging human diploid cells.

The rate of rejoining of DNA strand breaks induced by 10 krad of gamma-irradiation has been studied in normal human diploid skin fibroblasts and in skin fibroblasts from six patients with symptoms of progeria. Although slightly more rapid in very early passage, the repair rate in normal cells was similar throughout most of their life span in vitro. The appearance of cells with reduced repair capacity was evident as the cultures became senescent. The progeric fibroblasts varied greatly in their response to irradiation. The rate of repair was greatly reduced in two strains, whereas in two others extensive DNA degradation was consistently observed in unirradiated cells. Degradation was apparently related to the radiation received from the incorporated radiolabel. Normal repair was seen in progeric fibroblasts transformed by SV40 virus.

Aging↗
PubMed1978

Differential inhibition of the rejoining of X-ray-induced DNA strand breaks in normal and transformed human fibroblasts treated with 1,3-bis(2-chloroethyl)-1-nitrosourea in vitro.

The effects of 1,3-bis(2-chloroethyl)-1-nitrosourea on the rejoining of X-ray-induced DNA strand breaks were examined in normal human fibroblasts (WI-38) and a simian virus 40-transformed derivative (VA-13) with the use of alkaline sucrose sedimentation. 1,3-Bis(2-chloroethyl)-1-nitrosourea was capable of partially inhibiting repair of X-ray-produced DNA strand breaks in both cell types when the drug was added to the culture medium immediately after X-irradiation. However, when 1,3-bis(2-chloroethyl)-1-nitrosourea exposure preceded X-ray by 1 hr, DNA repair was inhibited to a much greater extent than it was when 1,3-bis(2-chloroethyl)-1-nitrosourea followed X-ray. The inhibition of DNA repair by 1,3-bis(2-chloroethyl)-1-nitrosourea appeared to be complete in the transformed VA-13 cells, while only partial inhibition of repair was observed in the normal WI-38 cells.

Carmustine↗
PubMed1976

Fast neutron and x-ray induced single strand DNA breaks in cultured mammalian cells.

The relative biologic effectiveness (RBE) of fast neutrons in the production of single strand DNA breaks is 1.6 as compared to that of 250 kVp x rays. Monolayers of L-929 cells were treated with dinitrophenol during irradiation to prevent the DNA strands from rejoining; the extent of DNA damage was measured by the alkaline sucrose sedimentation method. The RBE for DNA damage is essentially the same as the RBE measured by cell survival methods.

Animals↗
PubMed1976

Properties of a DNA ligase mutant of Escherichia coli: introduction of strand breaks in DNA.

Strand breaks accumulated in the DNA of a temperature-sensitive DNA ligase mutant of Escherichia coli growing at the restrictive temperature, as detected by zone sedimentation through alkaline sucrose density gradients. The rate of strand breakage was increased by concomitant thymine starvation. Rifampicin and chloramphenicol inhibited the accumulation of strand breaks in the DNA. There was a correlation between the accumulation of strand breaks in the DNA and lethality, suggesting that such breaks are the basis for lethality at the restrictive temperature.

Chloramphenicol↗
PubMed1978

[Effect of B polA1- exrA- and recA-gene mutations on the reparation of single-strand DNA breaks induced by N-nitrosomethylurea].

The effect of different doses of N-methyl-N-nitrosourea (MNU) on a viability of bacterial cells with different defects in the systems of repair of UV-damages, and the MNU induction of single-strand DNA breaks (SS) were studied. The kinetics of both processes was investigated. There was a good correlation between the NMU sensitivity of bacterial cells and the number of SS in their DNAs. The most sensitive were the cells defective in DNA polymerase I. The optimal conditions for DNA repair in the strains under investigation were established. 90% of MNU-induced SS are repaired by DNA polymerase I and do not depend on protein synthesis. On the other hand, the exrA and recA dependent ways of SS repair depend on protein synthesis. The existence of an inducible recAexrA-dependent repair system of NMU-induced lesions in bacterial DNA is proposed.

DNA Repair↗
PubMed1978

Unrepaired DNA strand breaks in irradiated ataxia telangiectasia lymphocytes suggested from cytogenetic observations.

It is suggested here that the unusually high level of radiation-induced chromosome and chromatid-type aberrations in cells from patients with ataxia telangiectasia, compared with normals, is due to a significantly increased fraction of unrepaired double and single strand breaks. A hypothesis is proposed to explain how unrepaired and misrepaired DNA single or double strand breaks might be the basic lesion leading to the typical chromosome aberrations seen following X-irradiation of both normal or AT cells.

Ataxia Telangiectasia↗
PubMed1976

Characterization of DNA polymerase induced by bacteriophage T5 with DNA containing single strand breaks.

DNA polymerase induced by bacteriophage T5 was purified and characterized using mainly circular duplex DNA of bacteriophage PM2 with single strand breaks formed by DNase I action. A purification procedure is described which has consistently yielded DNA polymerase preparations with only one detectable protein band after polyacrylamide gel electrophoresis of either native protein in Tris-glyase preparations utilized both denatured DNA and nicked DNA as primer-templates, although at 37 degrees the activity with denatured DNA was much greater. Polymerase activities with both kinds of primer-templates were shown to be associated with one phage-induced protein. DNA synthesis with nicked DNA as primer-template increased with increasing numbers of single strand breaks. Essentially all such breaks were repairable by ligase. Alkaline sucrose gradient centrifugation showed that synthesis occurred with the strand which had a single strand break as a primer yielding DNA longer than one phage DNA unit length. Newly synthesized DNA was covalently linked to the primer strand. Thus the synthesis very likely occurred by strand displacement; this is supported by electron micrographs shown in the Appendix.

Coliphages↗
PubMed1979

Induction and repair of DNA strand breaks in cultured mammalian cells following fast neutron irradiation.

Induction and repair of DNA breaks following irradiation with NIRS cyclotron neutrons were studied in cultured mammalian cells (L5178Y) in comparison to those following gamma-rays. The yield of the total single-strand breaks, 3'OH terminals and sites susceptible to S1 endonuclease following fast neutrons was found to be approximately 50 per cent of that following gamma-irradiation. On the other hand, the yield of double-strand breaks was slightly higher after fast neutrons than after gamma-rays. The percentage of the total single-strand breaks remaining unrejoined at 3 hours after post-irradiation incubation was found to be distinctly higher after the fast neutrons than after gamma-rays. The neutron-induced damage appears to carry a higher proportion of alkali-labile lesions compared to gamma-rays. It was concluded that the increase in the yield of double-strand breaks and of unrejoinable breaks is responsible for a high r.b.e. of the cyclotron neutrons.

Animals↗
PubMed1978

Non-enzymatic DNA strand breaks induced in mammalian cells by fluorescent light.

Fluorescent light (5.4 J . m-2 . s-1) induces 0.041 single-strand breaks per 10(8) daltons per h in the DNA of cultured Chinese hamster cells (4.8 . 10(-6) breaks per 10(8) daltons per J . m-2). The breaks are induced at 1 degrees C and hence are not likely to be the result of endonuclease incision. When the cells are incubated at 37 degrees C, the breaks are rejoined within 2 h. At least two lesions are responsible for the observed effects. One lesion has the ability to break DNA subsequently treated with alkali but is neither toxic nor mutagenic. This lesion is produced by light of wavelength greater than approx. 350 nm. The other lesion(s) produce mutagenicity and/or toxicity, but do not necessarily produce strand breaks. These lesion(s) are produced by light of wavelength less than 350 nm.

4-Aminobenzoic Acid↗
PubMed1979

Radiation-induced DNA strand breaks in deoxygenated aqueous solutions. The formation of altered sugars as end groups.

Gamma irradiation of DNA in deoxygenated, N2O-saturated aqueous solution leads to three bound altered sugars present as end groups in broken DNA strands. These sugars are linked to the DNA by phosphoric acid ester bonds. Two of the end groups have the structures (4) and (5). (Formula: see text) The third end group after dephosphorylation has structure (3). The formation of the bound sugars (4) and (5) is explained by a mechanism postulated earlier for the formation of free altered sugars. Except for the phosphoric acid ester linkage, the free altered sugars have the same chemical structures as the bound altered sugars.

Chemical Phenomena↗