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Estimation of significance of AlkB and AlkA proteins in DNA repair in Escherichia coli model

Sokołowska B., Maciejewska A. M., Jóźwik A., Kuśmierek J. T.

Journal of Medical Informatics & Technologies

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2011

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Vol. 17

321--326

EN

The paper concerns estimation of significance of differences of mutagenesis level between the wild-type strain (wt) and its derivatives which differ in DNA repair ability, namely alkA and alkB strain, devoided AlkA glycosylase and AlkB dioxygenase activity, respectively. The strains were analyzed for their ability to repair 1,N6-ethenoadenine (εA) - chloroacetaldehyde adduct to DNA. The analysis was done using classical statistical and pattern recognition methods. The obtained results confirmed that AlkB dioxygenase plays the most important role in εA repair in E. coli in the experimental modeling.

2

Charge transfer in DNA and repair of oxidative damage

Męczyńska S., Szumiel I.

Nukleonika

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2009

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Vol. 54, No. 1

11-16

EN

The possibility of a biological role of an unusual function of DNA sequences is discussed, namely, signaling by charge transfer within chromatin. Although a general conclusion on its biological significance is premature, the idea of charge transfer accompanying repair of some types of oxidative DNA damage is based on sound experimental data. Both physical and chemical experiments reviewed here provided results indicating that DNA duplex under certain conditions (among them – hydration) – can behave as narrow band gap semiconductor. With the use of model molecules it was shown that charge transfer most probably occurs by hopping between guanine residues and tunneling through thymine-adenine (TA) base pairs. Charge transfer is nucleotide sequence and distance dependent. Furthermore, the pi-stacked base pairs must be perfectly matched to mediate charge transfer and in a damaged double helix this condition is not fulfilled. Hence, the possibility that charge transfer takes place in oxidatively damaged DNA after UV or X-irradiation and it becomes interrupted by mismatched base pairs, thus signaling the mismatch or strand break to the repair machinery. Function of base damage repair enzymes which contain [4Fe-4S] clusters is discussed in this context.

3

Application of the k-NN classifier for mutagenesis tests. Recognition of wild type and defective in DNA repair bacterial strains on the basis of adaptive response to alkylating agents

Maciejewska A. M., Jóźwik A., Kuśmierek J. T., Sokołowska B.

Biocybernetics and Biomedical Engineering

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2008

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Vol. 28, no. 3

45-50

EN

The k-Nearest Neighbor classifier (k-NN) was applied to differentiate two bacterial strains, the wild type and its mug derivative. Bacterial cells were exposed to different concentrations of chloroacetaldehyde and studied under two different conditions, i.e. with and without induction of an adaptive response. We evaluated the influence of adaptation on the wt and mug strains by estimating the probability of misclassification to the class: no adaptation or adaptation. We have also checked differentiation between wt and mug, separately for adapted and non-adapted conditions. Our results confirm the usefulness of the k-NN classifier as a tool for statistical analysis of results of mutagenesis tests.

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Effects of an antimutagen of 1,4-dihydropyridine series on cell survival and DNA damage in L5178Y murine sublines

Dalivelya O., Savina N., Kuzhir T., Buraczewska I., Wojewódzka M., Szumiel I.

Nukleonika

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2006

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Vol. 51, nr 3

141-146

EN

In a series of studies it was shown that 1,4-dihydropyridine derivatives (1,4-DHP) show antimutagenic and anticlastogenic properties and accelerate repair of oxidant and ionising radiation generated DNA damage. Here, effects of one of 1,4-DHP compounds (sodium 3,5-bis-ethoxycarbonyl-2,6-dimethyl-1,4-dihydropyridine-4-carboxylate denoted as DHP) in X-irradiated L5178Y cells (murine lymphoma sublines, LY-R and LY-S) are reported. DHP treatment 1 h before, during and after X-irradiation gave a radioprotective effect in double strand break (DSB) repair competent LY-R cells: there was an increase in post-irradiation proliferation and cell viability as well as a slight acceleration of break rejoining as measured by the neutral comet assay. In the radiosensitive LY-S cells with impaired non-homologous end-joining system, the radioprotective effect was seen as enhanced growth and viability. There was, however, no effect on the DSB repair rate. Notably, there was no dependence of the biological effects on DHP concentration in the range of concentrations studied (1 nM - 100 mM), suggesting an all-or-none effect, as in cellular signaling induction observed in radioadaptation or bystander effect. We assume that DHP acts by decreasing fixation of radiation inflicted DNA damage, among others, by increasing the rate of DNA repair and enhancing the efficiency of checkpoint control. Direct confirmation of this assumption is necessary.

5

Application of ionizing radiation in studies of biomarkers of individual susceptibility

Cebulska-Wasilewska A.

Nukleonika

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2005

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Vol. 50,suppl.2

3-8

EN

Human biomonitoring, as a tool to identify health risk from environmental exposures, has gained increasing interest especially in the areas of cancer risk assessment and diseases treatment. Chromosome aberrations resulting from direct DNA breakage or from inhibition of DNA repair or synthesis, measured in peripheral blood lymphocytes, have been used successfully in the assessment of health risk associated to environmental genotoxic exposures. A faster but sensitive and reliable method for detection of DNA damage, or DNA repair capacity, might be crucial to many fields from molecular epidemiology and toxicology to preventive and clinical medicine. There are reports that results of DNA measures with the use of single cell gel electrophoresis (SCGE) correlate, on the one hand, with physical measures of genotoxins, and on the other hand, with cytogenetic damage that is a biomarker associated to the alteration of the health risk. This review is based on studies in which exposure to radiation was applied as a challenging treatment and DNA damage induced and repaired was analyzed with the use of the alkaline version of SCGE assay. Results from studies on susceptibilities and repair competence carried out in various groups of exposed workers, controls, and cancer patients (more than 700 donors) show variability between donors both in a response to challenging treatment and in the efficiency of repair process. Influences of the occupational exposures and factors depending on genotypes or life style on cellular capacities are observed. Discussed results suggest that study in vitro with the challenging cells by radiation exposure and measuring, with the SCGE assay, the DNA damage before and after repair, may develop a good biomarker of the individual susceptibility to various genotoxins and exposures (environmental, occupational, therapeutic). Such a biomarker may have a potential use in a molecular epidemiology and preclinical identification.

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The bystander effect: is reactive oxygen species the driver?

Szumiel I.

Nukleonika

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2003

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Vol. 48, nr 3

113-120

EN

The paper reviews selected examples of the bystander effect, such as clonogenic survival decrease, chromosomal aberrations and mutations. The similarities and differences between the biological effects in directly targeted and bystander cells are briefly discussed. Also reviewed are the experimental data which support the role of reactive oxygen species (ROS), especially *O2-, as mediators of the bystander effect. Endogenously generated ROS, due to activation of NAD(P)H oxidases, play a key role in the induction of DNA damage in bystander cells. All the observed effects in bystander cells, such as alterations in gene expression patterns, chromosomal aberrations, sister chromatid exchanges, mutations, genome instability, and neoplastic transformation are the consequence of DNA damage.

7

How do marine bacteria produce light, why are they luminescent, and can we employ bacterial bioluminescence in aquatic biotechnology?

Węgrzyn G., Czyż A.

Oceanologia

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2002

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No. 44 (3)

291-305

EN

Bioluminescence, the phenomenon of light production by living organisms, occurs in forms of life as various as bacteria, fungi and animals. Nevertheless, light-emitting bacteria are the most abundant and widespread of luminescent organisms. Interestingly, most species of such bacteria live in marine environments. In this article, the biochemical mechanism of bacterial luminescence and its genetic regulation are summarized. Although the biochemistry and genetics of light emission by cells have been investigated in detail, the biological role of bacterial luminescence has remained obscure. Here, we discuss recent discoveries that shed new light on this problem. Finally, we provide examples of how bacterial luminescence can be employed in marine biotechnology, especially in the detection of toxic and mutagenic pollution in aquatic environments.

8

Histone H2AX in DNA repair

Lewandowska H., Szumiel I.

Nukleonika

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2002

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Vol. 47, nr 4

127-131

EN

The paper reviews the recent reports on the role of the phosphorylated histone H2AX (gamma-H2AX). The modification of this histone is an important part of the cellular response to the induction of DNA double strand breaks (DSB) by ionising radiation and other DSB-generating factors. In irradiated cell the modification is carried out mainly by ATM (ataxia- -telangiectasia mutated) kinase, the enzyme that starts the alarm signalling upon induction of DSB. gamma-H2AX molecules are formed within 1 3 min after irradiation and form foci at the sites of DSB. This seems to be necessary for the recruitment of repair factors that are later present in foci of damaged nuclei. Modification of a constant percentage of H2AX molecules per DSB takes place, corresponding to chromatin domains of megabase pairs of DNA.

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"No Strain, No Gain: " Studies in the Mechanism of a DNA Repair Enzyme

Blackburn G., Walcher G.

Polish Journal of Chemistry

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2001

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Vol. 75, nr 8

1183-1194

EN

The presence of uracil in DNA occurs either as a result of the mis-incorporation of dUTP in place of dTTP or by deamination of deoxycytidine to give deoxyuridine and is pro-mutagenic. Some 500 such lesions are repaired per cell per day in man. The first enzyme in the repair pathway is uracil DNA glycohydrolase, UDG, which cleaves the glycosylic bond in deoxyuridine in DNA. It shows a rate acceleration of 1012 and specificity for uracil of at least 107 with respect to cytosine or thymine bases. Its mechanism of action has been revealed through the X-ray crystal structure of a transition-state analogue bound in the enzyme active site and is clearly a dissociative, SN1 type process.