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1.
Sylvie Elsen Véronique Collin-Faure Xavier Gidrol Claudie Lemercier 《Cellular and molecular life sciences : CMLS》2013,70(22):4385-4397
Highly hazardous DNA double-strand breaks can be induced in eukaryotic cells by a number of agents including pathogenic bacterial strains. We have investigated the genotoxic potential of Pseudomonas aeruginosa, an opportunistic pathogen causing devastating nosocomial infections in cystic fibrosis or immunocompromised patients. Our data revealed that infection of immune or epithelial cells by P. aeruginosa triggered DNA strand breaks and phosphorylation of histone H2AX (γH2AX), a marker of DNA double-strand breaks. Moreover, it induced formation of discrete nuclear repair foci similar to gamma-irradiation-induced foci, and containing γH2AX and 53BP1, an adaptor protein mediating the DNA-damage response pathway. Gene deletion, mutagenesis, and complementation in P. aeruginosa identified ExoS bacterial toxin as the major factor involved in γH2AX induction. Chemical inhibition of several kinases known to phosphorylate H2AX demonstrated that Ataxia Telangiectasia Mutated (ATM) was the principal kinase in P. aeruginosa-induced H2AX phosphorylation. Finally, infection led to ATM kinase activation by an auto-phosphorylation mechanism. Together, these data show for the first time that infection by P. aeruginosa activates the DNA double-strand break repair machinery of the host cells. This novel information sheds new light on the consequences of P. aeruginosa infection in mammalian cells. As pathogenic Escherichia coli or carcinogenic Helicobacter pylori can alter genome integrity through DNA double-strand breaks, leading to chromosomal instability and eventually cancer, our findings highlight possible new routes for further investigations of P. aeruginosa in cancer biology and they identify ATM as a potential target molecule for drug design. 相似文献
2.
Summary Poison oak urushiol, a mixture of 3-alk(en)ylcatechol derivatives was found to mediate DNA strand scission in the presence of oxygen and with copper(II) chloride as a catalyst. The reactionis believed to occur via activated reduced oxygen produced during oxidation of the catechol into itso-quinone derivative. 相似文献
3.
The search for the right partner: Homologous pairing and DNA strand exchange proteins in eukaryotes 总被引:13,自引:0,他引:13
W. -D. Heyer 《Cellular and molecular life sciences : CMLS》1994,50(3):223-233
Finding the right partner is a central problem in homologous recombination. Common to all models for general recombination is a homologous pairing and DNA strand exchange step. In prokaryotes this process has mainly been studied with the RecA protein ofEscherichia coli. Two approaches have been used to find homologous pairing and DNA strand exchange proteins in eukaryotes. A biochemical approach has resulted in numerous proteins from various organisms. Almost all of these proteins are biochemically fundamentally different from RecA. The in vivo role of these proteins is largely not understood. A molecular-genetical approach has identified structural homologs to theE. coli RecA protein in the yeastSaccharomyces cerevisiae and subsequently in other organisms including other fungi, mammals, birds, and plants. The biochemistry of the eukaryotic RecA homologs is largely unsolved. For the fungal RecA homologs (S. cerevisiae RAD51, RAD55, RAD57, DMC1; Schizosaccharomyces pombe rad51; Neurospora crassa mei3) a role in homologous recombination and recombinational repair is evident. Besides recombination, homologous pairing proteins might be involved in other cellular processes like chromosome pairing or gene inactivation. 相似文献
4.
Exposure to estrogens is a risk factor for breast and other human cancers. Initiation of breast, prostate and other cancers
has been hypothesized to result from reaction of specific estrogen metabolites, catechol estrogen-3,4-quinones, with DNA to
form depurinating adducts at the N-7 of guanine and N-3 of adenine by 1,4-Michael addition. The catechol of the carcinogenic
synthetic estrogen hexestrol, a hydrogenated derivative of diethylstilbestrol, is metabolized to its quinone, which reacts
with DNA to form depurinating adducts at the N-7 of guanine and N-3 of adenine. The catecholamine dopamine and the metabolite
catechol (1,2-dihydroxybenzene) of the leukemogen benzene can also be oxidized to their quinones, which react with DNA to
form predominantly analogous depurinating adducts. Apurinic sites formed by depurinating adducts are converted into tumor-initiating
mutations by error-prone repair. These mutations could initiate cancer by estrogens and benzene, and Parkinson's disease by
the neurotransmitter dopamine. These data suggest a unifying molecular mechanism of initiation for many cancers and neurodegenerative
diseases and lay the groundwork for designing strategies to assess risk and prevent these diseases.
Received 4 September 2001; received after revision 28 November 2001; accepted 2 December 2001 相似文献
5.
Mosesso P Piane M Palitti F Pepe G Penna S Chessa L 《Cellular and molecular life sciences : CMLS》2005,62(4):485-491
The cells of an ataxia-oculomotor apraxia type 1 (AOA1) patient, homozygous for a new aprataxin mutation (T739C), were treated with camptothecin, an inhibitor of DNA topoisomerase I which induces DNA single-strand breaks. DNA damage was evaluated by cytogenetic analysis of chromosomal aberrations. The results obtained showed marked and dose-related increases in induced chromosomal aberrations in the patient and her heterozygous mother compared to the intrafamilial wild-type control. The alkaline comet assay confirmed this pattern. Moreover, the AOA1 cells did not show hypersensitivity to ionizing radiation, i.e. X-rays. These findings clearly indicate the direct involvement of aprataxin in the DNA single-strand-break repair machinery.Received 6 October 2004; received after revision 24 November 2004; accepted 28 December 2004P. Mosesso and M. Piane contributed equally to this work. 相似文献
6.
K. Shinozuka Y. Kikuchi C. Nishino A. Mori S. Tawata 《Cellular and molecular life sciences : CMLS》1988,44(10):882-885
Summary Flavonoids, (–)-epigallocatechin (1), myricetin (2) and quercetin (3), were investigated for inhibitory effects onE. coli DNA polymerase I and T7 bacteriophage RNA polymerase. In both DNA and RNA synthesis,1 and3 inhibited enzyme reactions by non-competitive and mixed type inhibition respecitively, with regard to template DNAs. Myricetin (2) inhibited DNA and RNA polymerase reactions by mixed type and competitive type inhibition, respectively, with template DNAs. It was suggested that2 interacts with covalently closed/circular DNA. 相似文献
7.
Y. Endo-Ichikawa H. Kohno R. Tokunaga Y. Yabusaki T. Sakaki H. Ohkawa S. Taketani 《Cellular and molecular life sciences : CMLS》1995,51(6):564-568
N-Oxidation of 4,4-methylene-bis(2-chloroaniline) (MBOCA) may lead to formation of DNA adducts. To determine if cytochrome P450s are involved in the formation of MBOCA derived-DNA adducts, yeast strains expressing rodent P450s were exposed to MBOCA, and32P-postlabelling of nucleotides from yeast genomic DNA was done. Chromatographic analysis on PEI cellulose showed that, upon exposure to MBOCA for 1 h, nine DNA adducts were formed in yeast expressing phenobarbital-inducible rabbit P450 2B5. With a 4-h-exposure, all adducts increased in parallel. In cell-free experiments, the incubation of MBOCA with phenobarbital-induced rat microsomal fraction followed by incubation with thymus DNA, led to the formation of more than ten DNA adducts. When yeast expressing 3-methylcholanthrene-inducible rat P450 1A1 was exposed to MBOCA, one major and two minor adducts were formed. No adducts were detected in control yeast. These results show that recombinant rabbit P450 2B5 exhibits a potential activation of MBOCA and that rat P450 1A1 has some effect. The use of yeast expressing recombinant P450s and the technique of32P-postlabelling facilitates a simple search for chemicals with carcinogenic potential. 相似文献
8.
S. A. Komarov 《Cellular and molecular life sciences : CMLS》1985,41(6):746-747
Summary Incorporation of3H-thymidine (3HTdr) into the nuclei of myofibril-containing myofibers of larvae of the silkworm,Bombyx mori, was shown by means of light microscope (LM) and electron-microscope (EM) autoradiography. The number of DNA-synthesizing myonuclei attains 42% 12–18 h after each molt. Thus in the developing silkworm DNA replication and myofibrillogenesis are coexisting and not mutually exclusive processes as is the rule in vertebrate somatic myogenesis. 相似文献
9.
The correct repair of double-strand breaks (DSBs) is essential for the genomic integrity of a cell, as inappropriate repair
can lead to chromosomal rearrangements such as translocations. In many hematologic cancers and sarcomas, translocations are
the etiological factor in tumorigenesis, resulting in either the deregulation of a proto-oncogene or the expression of a fusion
protein with transforming properties. Mammalian cells are able to repair DSBs by pathways involving homologous recombination
and nonhomologous end-joining. The analysis of translocation breakpoints in a number of cancers and the development of model
translocation systems are beginning to shed light on specific DSB repair pathway(s) responsible for the improper repair of
broken chromosomes.
Received 19 June 2001; received after revision 6 September 2001; accepted 11 September 2001 相似文献
10.
Summary Analysis of chromosomes from cells treated with adriamycin during G2 and S phases showed a high frequency of isochromatid-type of breaks, in addition to the expected chromatid breaks. These are interpreted as independent breaks on sister chromatids because of preferential effects of the drug in specific chromosome regions. The break points are likely to be different, but morphologically such breaks would be indistinguishable from isochromatid or chromosome breaks.Supported in part by NO1-CM-53773 Division of Cancer Treatment NCI, Bethesda, Maryland, and by Research Grant No. VC-21 from American Cancer Society. 相似文献
11.
Poly-ADP-ribosylation in health and disease 总被引:6,自引:0,他引:6
12.
E. Petitpierre J. M. Gatewood C. W. Schmid 《Cellular and molecular life sciences : CMLS》1988,44(6):498-499
Summary A 142 base-pair satellite DNA from the mealworm beetle,Tenebrio molitor, has been cloned and sequenced. The satellite DNA is revealed by making a restriction digest of genomic DNA with either EcoRI or Hinfl, and constitutes approximately 49% of the genomic DNA. The presence of huge amounts of satellite DNA correlates well with the prominent blocks of heterochromatin found in tenebrionid beetles. A similar restriction digest ofXanthogaleruca luteola genomic DNA does not release a prominent satellite component. 相似文献
13.
Le Bouffant R Cormier P Cueff A Bellé R Mulner-Lorillon O 《Cellular and molecular life sciences : CMLS》2007,64(13):1723-1734
DNA integrity checkpoint control was studied in the sea urchin early embryo. Treatment of the embryos with genotoxic agents
such as methyl methanesulfonate (MMS) or bleomycin induced the activation of a cell cycle checkpoint as evidenced by the occurrence
of a delay or an arrest in the division of the embryos and an inhibition of CDK1/cyclin B activating dephosphorylation. The
genotoxic treatment was shown to induce DNA damage that depended on the genotoxic concentration and was correlated with the
observed cell cycle delay. At low genotoxic concentrations, embryos were able to repair the DNA damage and recover from checkpoint
arrest, whereas at high doses they underwent morphological and biochemical changes characteristic of apoptosis. Finally, extracts
prepared from embryos were found to be capable of supporting DNA repair in vitro upon incubation with oligonucleotides mimicking damage. Taken together, our results demonstrate that sea urchin early embryos
contain fully functional and activatable DNA damage checkpoints. Sea urchin embryos are discussed as a promising model to
study the signaling pathways of cell cycle checkpoint, DNA repair and apoptosis, which upon deregulation play a significant
role in the origin of cancer.
Received 10 April 2007; accepted 23 April 2007 相似文献
14.
Microtubule associated protein tau binds to double-stranded but not single-stranded DNA 总被引:3,自引:0,他引:3
Hua Q He RQ Haque N Qu MH del Carmen Alonso A Grundke-Iqbal I Iqbal K 《Cellular and molecular life sciences : CMLS》2003,60(2):413-421
Tau, a major microtubule-associated protein of the neuron, which is known to promote the assembly of and to stabilize microtubules,
has also been seen associated with chromatin in neuronal cell lines, but its role in this subcellular compartment is still
unknown. In this study, the binding of tau to DNA was investigated using the electrophoretic mobility shift assay. Using polynucleotide
as probe, we found that tau bound to double-stranded but not to single-stranded DNA. Formation of tau-polynucleotide complex
was disrupted by alkaline pH and a high concentration of NaCl, but was not affected by dithiothreitol. Electron microscopy
revealed that the protein associated with the nucleic acid in a necklacelike manner. DNA-cellulose chromatography and radioimmunodot-blot
analyses showed that calf thymus histones VI-S, VII-S and VIII-S could replace both recombinant human brain tau352 (tau-23) and tau441 (tau-40) from DNA. Thus, tau appears to bind to DNA reversibly in the presence of histones.
Received 24 November 2002; received after revision 28 December 2002; accepted 30 December 2002
RID="*"
ID="*"Corresponding author. 相似文献
15.
Dave JR Connors RA Genovese RF Whipple RA Chen RW DeFord SM Moran AV Tortella EC 《Cellular and molecular life sciences : CMLS》2007,64(21):2823-2828
The objective of this study was to determine levels of DNA fragmentation in blood leukocytes and parietal cortex from guinea
pigs following repeated lowlevel exposure to the chemical warfare nerve agent (CWNA) sarin. Guinea pigs were injected (s.c.)
once a day for 10 days with saline, or 0.1, 0.2, or 0.4 LD50 (50% mean lethal dose) sarin dissolved in sterile physiological saline. Blood and parietal cortex was collected after injection
at 0, 3, and 17 days recovery and evaluated for DNA fragmentation using single-cell gel electrophoresis (Comet assay). Cells
were imaged using comet analysis software and three parameters of DNA fragmentation measured: tail length, percent DNA in
the tail, and tail moment arm. Repeated low-dose exposure to sarin produced a dose-dependent response in leukocytes at 0 and
3 days post-exposure. There was a significant increase in all measures of DNA fragmentation at 0.2 and 0.4 LD50, but not at 0.1 LD50. There was no significant increase in DNA fragmentation in any of the groups at 17 days post-exposure. Sarin did not produce
a systematic dose-dependent response in parietal cortex at any of the time points. However, significant increases in DNA fragmentation
at 0.1 and 0.4 LD50 were observed at 0 and 3 days post-exposure. All measures of DNA fragmentation in both leukocytes and neurons returned to
control levels by 17 days post-exposure, indicating a small and non-persistent increase in DNA fragmentation following repeated
low-level exposure to sarin.
Received 23 July 2007; received after revision 23 August 2007; accepted 3 September 2007
Research was conducted in compliance with the Animal Welfare Act, and other Federal statutes and regulation relating to animals
and experiments involving animals and adheres to the principles
stated in the Guide for the Care and Use of Laboratory Animals, NIH publication 85-23. The views of the authors do not purport
to reflect the position of the Department of the Army or the Department of Defense (para 4-3), AR 360–365. 相似文献
16.
R. Matthey 《Cellular and molecular life sciences : CMLS》1946,2(12):497-498
Summary The chromosomal sets of five species ofPerlodidæ (Plecoptera) are given in the present paper. The sexual chromosomes belong to three distinct types:X-O,X
1-X
2,X
1-X
2-X
3. The author shows that these three types are likely derived from the most primitive patternX-Y, by translocation and inversion. 相似文献
17.
Welcome the Family of FANCJ-like Helicases to the Block of Genome Stability Maintenance Proteins 总被引:1,自引:0,他引:1
Y. Wu A. N. Suhasini R. M. Brosh Jr. 《Cellular and molecular life sciences : CMLS》2009,66(7):1209-1222
The FANCJ family of DNA helicases is emerging as an important group of proteins for the prevention of human disease, cancer,
and chromosomal instability. FANCJ was identified by its association with breast cancer, and is implicated in Fanconi Anemia.
Proteins with sequence similarity to FANCJ are important for maintenance of genomic stability. Mutations in genes encoding
proteins related to FANCJ, designated ChlR1 in human and Chl1p in yeast, result in sister chromatid cohesion defects. Nematodes
mutated in dog-1 show germline as well as somatic deletions in genes containing guanine-rich DNA. Rtel knockout mice are embryonic lethal, and embryonic stem cells show telomere loss and chromosomal instability. FANCJ also shares
sequence similarity with human XPD and yeast RAD3 helicases required for nucleotide excision repair. The recently solved structure
of XPD has provided new insight to the helicase core and accessory domains of sequence related Superfamily 2 helicases. The
functions and roles of members of the FANCJ-like helicase family will be discussed.
Received 17 September 2008; received after revision 24 October 2008; accepted 28 October 2008 相似文献
18.
M. Tamaro S. Venturini C. Eftimiadi C. Monti-Bragadin 《Cellular and molecular life sciences : CMLS》1977,33(3):317-319
Summary The cis and trans isomer of PtCl2(NH3)2, cis-Pt(cpa)2Cl2 and 2 platinum pyrimidine blues have been used in a number of bacterial tests indicative of their interaction with bacterial DNA.This investigation was supported by a grant from C.N.R., Rome. We thank Mrs S. Saincich for skilful technical assistance. 相似文献
19.
J. Schaller U. Kämpfer S. Schürch L. Kuhn-Nentwig S. Haeberli W. Nentwig 《Cellular and molecular life sciences : CMLS》2001,58(10):1538-1545
CSTX-9 (68 residues, 7530.9 Da) is one of the most abundant toxic polypeptides in the venom of the wandering spider Cupiennius salei. The amino acid sequence was determined by Edman degradation using reduced and alkylated CSTX-9 and peptides generated by
cleavages with endoproteinase Asp-N and trypsin, respectively. Sequence comparison with CSTX-1, the most abundant and the
most toxic polypeptide in the crude spider venom, revealed a high degree of similarity (53% identity). By means of limited
proteolysis with immobilised trypsin and RP-HPLC, the cystine-containing peptides of CSTX-9 were isolated and the disulphide
bridges were assigned by amino acid analysis, Edman degradation and nanospray tandem mass spectrometry. The four disulphide
bonds present in CSTX-9 are arranged in the following pattern: 1-4, 2-5, 3-8 and 6-7 (Cys6-Cys21, Cys13-Cys30, Cys20-Cys48, Cys32-Cys46). Sequence comparison of CSTX-1 with CSTX-9 clearly indicates the same disulphide bridge pattern, which is also found in
other spider polypeptide toxins, e.g. agatoxins (ω-AGA-IVA, ω-AGA-IVB, μ-AGA-I and μ-AGA-VI) from Agelenopsis aperta, SNX-325 from Segestria florentina and curtatoxins (CT-I, CT-II and CT-III) from Hololena curta. CSTX-1/CSTX-9 belong to the family of ion channel toxins containing the inhibitor cystine knot structural motif. CSTX-9,
lacking the lysine-rich C-terminal tail of CSTX-1, exhibits a ninefold lower toxicity to Drosophila melanogaster than CSTX-1. This is in accordance with previous observations of CSTX-2a and CSTX-2b, two truncated forms of CSTX-1 which,
like CSTX-9, also lack the C-terminal lysine-rich tail.
Received 23 July 2001; accepted 31 July 2001 相似文献
20.
C. S. Champion D. Kumar M. T. Rajan K. S. Jagannatha Rao M. A. Viswamitra 《Cellular and molecular life sciences : CMLS》1998,54(5):488-496
Spectroscopic study of the interactions of metal ions, Co, Mn, Mg and Al with d(GCCCATGGGC) and d(CCGGGCCCGG) revealed the
following. Metal ions Mn, Al and Mg at the lowest concentrations enhanced the t
m of oligomers, whereas Mn and Mg at higher concentrations decreased the t
m . Co enhanced the t
m of oligomers at higher concentrations. The studies have also indicated that Mn at lower concentrations displaced EtBr fluorescence,
Mg and Co at moderate concentrations and Al only at higher concentrations. Addition of Co, Mn, Mg and Al altered the bands
of the circulars dichroism (CD) spectra of the oligomers in a concentration-dependent manner. The CD spectra of d(GCCCATGGGC)
and d(CCGGGCCCGG) indicated B and Z forms of DNA, respectively, in contrast to the A form observed in the crystal structures.
Mg and Co at different ionic strength induced Z–B transition in d(CCGGGCCCGG), while Al at higher concentrations induced a
Z–A transition. Mn did not induce any transition. This is the first report to show that Al causes structural transitions in
sequence-specific oligomers and has strong binding ability with GC-rich euchromatin oligomers.
Received 22 December 1997; received after revision 16 March 1998; accepted 16 March 1998 相似文献