Wyniki wyszukiwania

1

Inhibition of poly[ADP-ribose] polymerase activity affects its subcellular localization and DNA strand break rejoining

100%

Ryabokon N. I., Cieslar-Pobuda A., Rzeszowska-Wolny J.

Acta Biochimica Polonica

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2009

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tom 56

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nr 2

243-248

Poly(ADP-ribose) polymerase (PARP) plays a crucial role in DNA repair. Modulation of its activity by stimulation or inhibition is considered as a potentially important strategy in clinical practice, especially to sensitize tumor cells to chemo- and radiotherapy through inhibition of DNA repair. Here we studied the effect of the three PARP inhibitors, 5-iodo-6-amino-benzopyrone (INH2BP), 1,5-isoquinolinediol (1,5-dihydroxyisoquinolinediol (1,5-IQD) and 8-hydroxy-2-methylquinazolin-4-[3H]one (NU1025), and for two of them the efficiency in slowing the rejoining of DNA strand breaks induced by H2O2 was compared. Inhibition of PARP changed its intranuclear localization markedly; cells exposed to the inhibitor NU1025 showed a significant tendency to accumulate PARP in large foci, whereas in untreated cells its distribution was more uniform. The speed and efficiency of rejoining of H2O2-induced DNA strand breaks were lower in cells incubated with a PARP inhibitor, and the kinetics of rejoining were modulated in a different manner by each inhibitor. At a concentration of 100 µM the efficiency of the inhibitors could be ranked in the order NU1025 > IQD > INH2BP. The two first compounds were able to decrease the overall PARP activity below the level detected in control cells, while INH2BP showed up to 40% PARP activity after exposure to H2O2.

2

Poly(ADP-ribose) polymerase-1 is a novel nuclear target for cholinergic receptor signaling in the hippocampus

86%

Strosznajder R. P., Jesko H., Adamczyk A.

Journal of Physiology and Pharmacology. Supplement

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2005

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tom 56

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nr 4

209-213

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme involved in DNA repair and transcription regulation. The aim of this study was to investigate the role of PARP-1 in muscarinic cholinergic receptor signaling. Our data indicate that activation of muscarinic cholinergic receptors by carbachol (1mM) in the presence of GTPS evoked a significant enhancement of PARP activity in the adult rat hippocampus. Moreover, TMB-8 (10µM), an antagonist of inositol 1, 4, 5 trisphosphate (IP3) receptor prevented the activation of PARP-1, which indicates that IP3 /Ca2+ signaling is involved in this pathway. The diacylglycerol (DAG)-regulated protein kinase C (PKC) inhibitor (GF109203X) (1µM) only slightly enhanced PARP activity in hippocampal nuclear fractions, which suggests that DAG/ PKC is not involved in PARP activation.

3

Microbial host-mediated assays, a convenient method to investigate the biotransformation of xenobiotic compounds to genotoxins in vitro

86%

Knasmuller S., Szakmary A., Wottawa A.

Bulletin of the Polish Academy of Sciences. Biological Sciences

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1988

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tom 36

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nr 10-12

4

Small molecule inhibitors of DNA-PK for tumor sensitization to anticancer therapy

86%

Pospisilova M., Seifrtova M., Rezacova M.

Journal of Physiology and Pharmacology

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2017

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tom 68

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nr 3

5

Mutation in the CDC8 gene is RAD6 dependent in Saccharomyces cerevisiae

86%

Baranowska H., Zuk J.

Bulletin of the Polish Academy of Sciences. Biological Sciences

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1991

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tom 39

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nr 2

6

A new look at adaptive mutations in bacteria

86%

Janion C.

Acta Biochimica Polonica

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2000

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tom 47

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nr 2

This is a short survey of the adaptive mutation processes that arise in non- or slowly- dividing bacterial cells and includes: (i) bacterial models in which adaptive mutations are studied; (ii) the mutagenic lesions from which these mutations derive; (iii) the influence of DNA repair processes on the spectrum of adaptive mutations. It is proposed that in starved cells, likely as during the MFD phenomenon, lesions in tRNA suppressor genes are preferentially repaired and no suppressor tRNAs are formed as a result of adaptive mutations. Perhaps the most provocative proposal is (iv) a hypothesis that the majority of adaptive mutations are selected in a pre-apoptotic state where the cells are either mutated, selected, and survive, or they die.

7

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Inhibition of DNA repair by cadmium and lead in sheep lymphocytes: protective interaction of magnesium

86%

Stec J.

Bulletin of the Veterinary Institute in Puławy

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2000

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tom 44

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nr 2

The effects of magnesium on the genotoxicity of cadmium chloride and lead acetate were investigated. The DNA repair as the genotoxicity test was determined in cultured sheep lymphocytes treated with the heavy metals in combination with UV-induced DNA damage. Excision repair was performed by incorporation of [³H]-thymidine into DNA of lymphocytes synchronised with hydroxyurea in G₁/S phase. The results show that DNA repair was strongly affected by cadmium (Il) but only slightly in cells treated with lead, indicating rather mitogenic properties. Repair inhibition made by cadmium was restored after treatment of lymphocyte cultures with 0.4 mM. of magnesium chloride for six hours. In conclusion, genotoxicity of Cd or Pb to lymphocytic DNA was markedly decreased by the presence of Mg in culture media.

8

Poly[ADP-ribose] polymerase in base excision repair: always engaged, but not essential for DNA damage processing

86%

Allinson S. L., Dianova I. I., Dianov G. L.

Acta Biochimica Polonica

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2003

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tom 50

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nr 1

Poly(ADP-ribose) polymerase (PARP-1) is an abundant nuclear protein with a high affinity for single- and double-strand DNA breaks. Its binding to strand breaks promotes catalysis of the covalent modification of nuclear proteins with poly(ADP-ribose) synthesised from NAD+ . PARP-1-knockout cells are extremely sensitive to alkylating agents, suggesting the involvement of PARP-1 in base excision repair; however, its role remains unclear. We investigated the dependence of base excision repair pathways on PARP-1 and NAD+ using whole cell extracts derived from normal and PARP-1 deficient mouse cells and DNA substrates containing abasic sites. In normal extracts the rate of repair was highly dependent on NAD+ . We found that in the absence of NAD+ repair was slowed down 4-6-fold after incision of the abasic site. We also established that in extracts from PARP-1 deficient mouse cells, repair of both regular and reduced abasic sites was increased with respect to normal extracts and was NAD+ -independent, suggesting that in both short- and long-patch BER PARP-1 slows down, rather than stimulates, the repair reaction. Our data support the proposal that PARP-1 does not play a major role in catalysis of DNA damage processing via either base excision repair pathway.

9

HIV and human endogenous retroviruses: An hypothesis with therapeutic implications

86%

McIntosh E. M., Haynes R. H.

Acta Biochimica Polonica

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1996

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tom 43

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nr 4

The enzyme dUTP pyrophosphatase (dUTPase, EC 3.6.1.23) is essential for cellular DNA replication and cell viability by virtue of its role in reducing the availability of dUTP as a substrate for DNA polymerases. Several members of the onco- and lentivirus families of retroviruses encode dUTPases and mutant strains of these viruses defective in this enzyme exhibit suboptimal replication kinetics. Among the lentiviruses there exists a surprising phylogenetic discontinuity in the distribution of dUTPase genes: non-primate viruses (EIAV, CAEV, FIV, visna) contain such genes whereas the primate viruses (HIVs, SIVs) do not The reason for this difference is unknown. We suggest the following explanation: (1) the nuclear and mitochondrial compartmentalization of the mammalian dUTPase, combined with the cytoplasmic location of ribonucleotide reductase, leads to the net synthesis of dUTP, together with dCTP, dGTP and dATP in the cytoplasm; (2) this combination of dNTPs serves as a "toxic cocktail" for viral replication by virtue of its ability to promote the synthesis of uracil-substituted DNA; (3) many viruses have adapted to this challenge by encoding dUTPases that are free of normal cellular regulatory constraints; and (4) the fortuitous expression of a dUTPase encoded by one or more human endogenous retroviruses (HERVs) has led to the evolutionary loss of the putative ancestral dUTPase gene of primate lentiviruses. Thus, we propose that efficient replication of HIV in humans depends upon expression of a dUTPase encoded by an endogenous retrovirus. If this proposal is correct, then the entry of HIV into target cells is necessary, but not sufficient, for replication of the virus in humans.

10

DNA repair in drug resistance induced by fusion tyrosine kinases

86%

Blasiak J.

Cellular and Molecular Biology Letters

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2002

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tom 07

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nr Suppl.

11

Nickel impairs the repair of UV - and MNNG-damaged DNA

86%

Wozniak K., Blasiak J.

Cellular and Molecular Biology Letters

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2004

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tom 09

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nr 1

Nickel(II) is reported to be genotoxic, but the mechanisms underlying its genotoxicity are largely unknown. It can interfere with DNA repair and this may contribute to its genotoxicity. We studied the effect of nickel chloride on the repair of DNA damaged by UV radiation or N-methyl-N-nitro-N-nitrosoguanidine (MNNG) in human lymphocytes using the alkaline comet assay. Nickel(II) at 1 μM caused an accumulation of DNA breaks during repair incubation, which could follow from the inhibition of the polymerization/ligation step of UV-damaged DNA repair. On the other hand, nickel(II) inhibited the formation of transient DNA breaks brought by the repair process after incubation with MNNG at 5 μM, which might follow from interference with the recognition/incision step of excision repair. Additionally, nickel at 1 μM inhibited the activity of formamidopyrimidine-DNA glycosylase (Fpg) and 3-methyladenine-DNA glycosylase II (Alk A), enzymes involved in DNA excision repair. A decrease in endonuclease III (Endo III) activity was observed at 2 and 5 μM of nickel chloride. Our results suggest that nickel(II) at non-cytotoxic concentrations can inhibit various steps of DNA excision repair, and this may contribute to its genotoxicity.

12

Comparison of repair activity in different genomic regions

86%

Chakalova L., Russev G.

Acta Biochimica Polonica

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1998

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tom 45

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nr 1

We have developed a quantitative technique to determine repair activity at defined genomic regions. Cells were treated with hydroxyurea to inhibit the replicative DNA synthesis and were incubated with 5-bromodeoxyuridine (BrdUrd) to label the regions undergoing repair. In the course of the labelling, the regions that were more actively repaired would incorporate more BrdUrd than the regions that were less actively repaired. Thus the kinetics of BrdUrd incorporation in the different sequences would reflect the kinetics of reparation of the respective regions. The total BrdUrd-containing, repaired DNA was isolated by immunoprecipitation with anti-BrdUrd antibody, and after controlled sonication, it was used as a template in quantitative PCR in which the amount of the product was directly proportional to the amount of template. This approach was used to address the question whether DNA repair after UV irradiation occurs in an uniformly random manner, or with preferences for certain regions. We found that, in Ehrlich ascites tumor cells, the repair efficiency was higher at the 5' end of the mouse β-globin domain than in the rest of the domain.

13

Impact of DNA repair during the storage effect

86%

Murin G., Micieta K.

Prace Naukowe Uniwersytetu Śląskiego w Katowicach

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1998

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tom 1696

14

Repair of DNA alkylation damage

86%

Bouziane M., Miao F., Ye N., Holmquist G., Chyzak G., O'Connor T. R.

Acta Biochimica Polonica

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1998

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tom 45

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nr 1

Alkylation damage of DNA is one of the major types of insults which cells must repair to remain viable. One way alkylation damaged ring nitrogens are repaired is via the Base Excision Repair (BER) pathway. Examination of mutants in both BER and Nucleotide Excision Repair show that there is actually an overlap of repair by these two pathways for the removal of cytotoxic lesions in Escherichia coli. The enzymes removing damaged bases in the first step in the BER pathway are DNA glycosylases. The coding sequences for a number of methylpurine-DNA glycosylases (MPG proteins) were cloned, and a comparison of the amino-acid sequences shows that there are some similarities between these proteins, but nonetheless, compared to other DNA glycosylases, MPG proteins are more divergent. MPG proteins have been purified to homogeneity and used to identify their substrates ranging from methylating agents to deamination products to oxidatively damaged bases. The ligation-mediated polymerase chain reaction has been used to study the formation of alkylation damage, and its repair in mammalian cells. We have studied DNA damage in the PGK1 gene for a series of DNA alkylating agents including N-methyl-N'-nitro-N-nitrosoguanidine, Mechlorethamine, and Chlorambucil and shown that the damage observed in the PGK1 (phosphoglycerate kinase 1) gene depends on the alkylating agent used. This report reviews the literature on the MPG proteins, DNA glycosylases removing 3-methyladenine, and the use of these enzymes to detect DNA damage at the nucleotide level.

15

Relationship between DNA replication and DNA repair in human lymphocytes proliferating in vitro in the presence and in absence of mutagen

86%

Szyfter K., Wiktorowicz K., Wielgosz M. S., Zajaczek S., Kujawski M., Jaloszynski P., Czub M., Markowska J.

Journal of Applied Genetics

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1995

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tom 36

|

nr 4

The effects of mutagens on DNA replication and DNA repair were studied in peripheral blood lymphocytes (PBL) obtained from 21 healthy subjects, 2 samples from healthy heterozygote of Xeroderma pigmentosum (XP) and 2 samples from patient with clinically recognised XP. Inter-individual variations were found in DNA replication and in the level of spontaneous DNA repair measured under standard culture condition. Exposure of human PBL proliferating in vitro to B(a)P was followed by a partial inhibition of replicative DNA synthesis in all subjects and by an induction of DNA repair in healthy subjects. In XP patients DNA repair synthesis remained at the level attributed to spontaneous DNA repair. The response to mutagen varied individually. Results were analysed statistically. It was established that the studied indices of DNA synthesis correlate well with each other. The highest correlation was found between the levels of spontaneous and B(a)P-induced DNA repair. It is concluded that the level of spontaneous DNA repair is predictive for an estimation of cells ability to repair DNA damage. Inter-individual variations in the inhibition of DNA replication and in DNA repair synthesis are also dependent on the type of mutagen as shown by effects of other mutagens. Different effects of mutagen exposure on the inhibition of DNA replicative synthesis and induction of DNA repair can be explained by genetically controlled differences in the activity of enzymes responsible for mutagen processing and lesion removal.

16

DNA damage and repair in normal and neoplastic cells treated with adriamycin

86%

Anuszewska E. L., Gruber B.

Acta Biochimica Polonica

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1994

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tom 41

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nr 4

Adriamycin (ADR), a common antineoplastic drug, was used to study DNA repair synthesis, cell cytotoxicity and DNA single strand breaks in normal human fibroblasts — CLV98 and human melanoma cells — ME18. No repair synthesis was observed in ME18 and CLV98 cells exposed to adriamycin in concentrations up to 10~5 M. ME18 cells were less sensitive to ADR treatment than CLV98 cells. Adriamycin-induced DNA single strand breaks (at ADR concentration: 1 pg/ml) were incompletely repaired in ME18 cells and unrepaired in CLV98 cells within 24 h after drug removal. Within 48 h strand breaks were completely repaired in both kinds of cells. No repair of single strand breaks was observed in ME18 and CLV98 cells after drug treatment in the concentration of 5 Jig/ml.

17

A novel approach for identifying DNA repair pathways proteins using an evolutionary approach: Plasmodium falciparum case study

72%

Milanowska K., Wojtczak J.

BioTechnologia. Journal of Biotechnology Computational Biology and Bionanotechnology

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2016

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tom 97

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nr 4

18

The role of mutation frequency decline and SOS repair systems in methyl methanesulfonate mutagenesis

72%

Grzesiuk E.

Acta Biochimica Polonica

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1998

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tom 45

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nr 2

Methyl methanesulfonate (MMS) is an SN2 type alkylating agent which predominantly methylates nitrogen atoms in purines. Among the methylated bases 3meA and 3meG are highly mutagenic and toxic. The excision of these lesions leads to the formation of apurinic (AP) sites and subsequently to AT-->TA or GC-->TA transversions. The in vivo method based on phenotypic analysis of Arg+ revertants of Escherichia coli K12 and sensitivity to T4 nonsense mutants has been used to estimate the specificity of MMS induced mutations. In the E. coli arg-his-thr- (AB1157) strain MMS induces argE3(oc)-->Arg+ revertants of which 70-80% arise by supL suppressor formation as a result of AT-->TA transversions. The remaining 20-30% arise by supB and supE(oc) suppressor formation as a result of GC-->AT transitions. The level of AT-->TA transversions decreases during starvation. This is a consequence of action of the repair mechanism called mutation frequency decline. This system which is a transcription coupled variant of nucleotide excision repair was discovered in UV induced mutations. We describe the mutation frequency decline phenomenon for MMS mutagenesis. MMS is a very efficient inducer of the SOS response and a umuDC dependent mutagen. In MMS treated E. coli cells mutated in umuDC genes the class of AT-->TA transversions dramatically diminishes. A plasmid bearing UmuD(D')C proteins can supplement chromosomal deletion of umuDC operon: a plasmid harbouring umuD'C is more efficient in comparison to that harbouring umuDC. Moreover, plasmids isolated from MMS treated and transiently starved E. coli AB1157 cells harbouring umuD(D')C genes have shown the repair of AP sites by a system which involves the UmuD'C or at least UmuD' protein.

19

Bacterial DNA repair genesn and their eukaryotic homologues: 4. The role of nucleotide excision DNA repair [NER] system in mammalian cells

72%

Maddukuri L., Dudzinska D., Tudek B.

Acta Biochimica Polonica

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2007

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tom 54

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nr 3

The eukaryotic cell encounters more than one million various kinds of DNA lesions per day. The nucleotide excision repair (NER) pathway is one of the most important repair mechanisms that removes a wide spectrum of different DNA lesions. NER operates through two sub pathways: global genome repair (GGR) and transcription-coupled repair (TCR). GGR repairs the DNA damage throughout the entire genome and is initiated by the HR23B/XPC complex, while the CSB protein-governed TCR process removes DNA lesions from the actively transcribed strand. The sequence of events and the role of particular NER proteins are currently being extensively discussed. NER proteins also participate in other cellular processes like replication, transcription, chromatin maintenance and protein turnover. Defects in NER underlay severe genetic disorders: xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD).

20

Hyperthermia can differentially modulate the repair of doxorubicin-damaged DNA in normal and cancer cells

72%

Blasiak J., Widera K., Pertynski T.

Acta Biochimica Polonica

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2003

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tom 50

|

nr 1

Hyperthermia can modulate the action of many anticancer drugs, and DNA repair processes are temperature-dependent, but the character of this dependence in cancer and normal cells is largely unknown. This subject seems to be worth studying, because hyperthermia can assist cancer therapy. A 1-h incubation at 37°C of normal human peripheral blood lymphocytes and human myelogenous leukemia cell line K562 with 0.5 juM doxorubicin gave significant level of DNA damage as assessed by the alkaline comet assay. The cells were then incubated in doxorubicin-free repair medium at 37°C or 41°C. The lymphocytes incubated at 37°C needed about 60 min to remove completely the damage to their DNA, whereas at 41°C the time required for complete repair was shortened to 30 min. There was also a difference between the repair kinetics at 37°C and 41°C in cancer cells. Moreover, the kinetics were different in doxorubicin-sensitive and resistant cells. Therefore, hyperthermia may significantly affect the kinetics of DNA repair in drug-treated cells, but the magnitude of the effect may be different in normal and cancer cells. These features may be exploited in cancer chemotherapy to increase the effectiveness of the treatment and reduce unwanted effects of anticancer drugs in normal cells and fight DNA repair-based drug resistance of cancer cells.

Ograniczanie wyników

Inhibition of poly[ADP-ribose] polymerase activity affects its subcellular localization and DNA strand break rejoining

Poly(ADP-ribose) polymerase-1 is a novel nuclear target for cholinergic receptor signaling in the hippocampus

Microbial host-mediated assays, a convenient method to investigate the biotransformation of xenobiotic compounds to genotoxins in vitro

Small molecule inhibitors of DNA-PK for tumor sensitization to anticancer therapy

Mutation in the CDC8 gene is RAD6 dependent in Saccharomyces cerevisiae

A new look at adaptive mutations in bacteria

Inhibition of DNA repair by cadmium and lead in sheep lymphocytes: protective interaction of magnesium

Poly[ADP-ribose] polymerase in base excision repair: always engaged, but not essential for DNA damage processing

HIV and human endogenous retroviruses: An hypothesis with therapeutic implications

DNA repair in drug resistance induced by fusion tyrosine kinases

Nickel impairs the repair of UV - and MNNG-damaged DNA

Comparison of repair activity in different genomic regions

Impact of DNA repair during the storage effect