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1.
Mol Cell Endocrinol ; 257-258: 6-14, 2006 Sep 26.
Article in English | MEDLINE | ID: mdl-16859826

ABSTRACT

Chronic treatment of rats with acrylamide induces various tumors among which thyroid tumors are the most frequent. The aim of the present study was to develop an in vitro model of acrylamide action on thyroid cells to allow the investigation of the mechanism of this tumorigenic action. The first part of the study considered as targets, characteristics of thyroid metabolism, which could explain the thyroid specificity of acrylamide action: the cAMP mitogenic effect and the important H2O2 generation by thyroid cells. However, acrylamide did not modulate H2O2 or cAMP generation in the thyroid cell models studied. No effect on thyroid cell proliferation was observed in the rat thyroid cell line FRTL5. On the other hand, as shown by the comet assay, acrylamide induced DNA damage, as the positive control H2O2 in the PC Cl3 and FRTL5 rat thyroid cell lines, as well as in thyroid cell primary cultures. The absence of effect of acrylamide on H2AX histone phosphorylation suggests that this effect does not reflect the induction of DNA double strand breaks. DNA damage leads to the generation of mutations. It is proposed that such mutations could play a role in the carcinogenic effect of acrylamide. The mechanism of this effect can now be studied in this in vitro model.


Subject(s)
Acrylamide/toxicity , Carcinogenicity Tests/methods , DNA Damage/drug effects , Thyroid Gland/cytology , Thyroid Gland/drug effects , Thyroid Neoplasms/chemically induced , Adenocarcinoma, Follicular/chemically induced , Animals , Cell Culture Techniques , Cell Line , Cells, Cultured , Colforsin/pharmacology , Comet Assay/methods , Cyclic AMP/metabolism , Dogs , Dose-Response Relationship, Drug , Epoxy Compounds/pharmacology , Humans , Hydrogen Peroxide/analysis , Rats , Sheep , Thyrotropin/pharmacology
2.
J Virol Methods ; 121(2): 145-53, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15381351

ABSTRACT

B19 may cause mild to severe clinical manifestations. Owing to the remarkable tropism of B19 for red blood cell progenitors, there is a lack of satisfactory cell lines fully permissive for B19. Because the local oxygen pressure may influence viral replication, we used hypoxia to improve the sensitivity of our infectivity assay in order to link B19 DNA detected by PCR to the presence of infectious B19 particles in plasma. Plasma samples and the WHO International Standard for B19 DNA detection by PCR were used to infect the pluripotent human erythroid cell line KU812F under different oxygen pressures. Specific human anti-B19 IgG was found to reduce infectivity. Low oxygen pressure led to higher yields of infectious B19 progeny and to a higher level of viral transcription than observed under normoxia. This sensitive infectivity assay is a promising model for studying B19 biology, identifying neutralising antibodies, and evaluating new virus inactivation methods.


Subject(s)
Cell Hypoxia , Parvovirus B19, Human/growth & development , Capsid Proteins/antagonists & inhibitors , Cell Line , Erythroid Precursor Cells , Erythropoietin , Humans , Immunoglobulin G/pharmacology , Parvovirus B19, Human/pathogenicity , Time Factors , Virus Cultivation/methods
3.
J Virol ; 75(22): 11071-8, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11602746

ABSTRACT

The nonstructural protein NS1 of the autonomous parvovirus minute virus of mice (MVMp) is cytolytic when expressed in transformed cells. Before causing extensive cell lysis, NS1 induces a multistep cell cycle arrest in G(1), S, and G(2), well reproducing the arrest in S and G(2) observed upon MVMp infection. In this work we investigated the molecular mechanisms of growth inhibition mediated by NS1 and MVMp. We show that NS1-mediated cell cycle arrest correlates with the accumulation of the cyclin-dependent kinase (Cdk) inhibitor p21(cip1) associated with both the cyclin A/Cdk and cyclin E/Cdk2 complexes but in the absence of accumulation of p53, a potent transcriptional activator of p21(cip1). By comparison, MVMp infection induced the accumulation of both p53 and p21(cip1). We demonstrate that p53 plays an essential role in the MVMp-induced cell cycle arrest in both S and G(2) by using p53 wild-type (+/+) and null (-/-) cells. Furthermore, only the G(2) arrest was abrogated in p21(cip1) null (-/-) cells. Together these results show that the MVMp-induced cell cycle arrest in S is p53 dependent but p21(cip1) independent, whereas the arrest in G(2) depends on both p53 and its downstream effector p21(cip1). They also suggest that induction of p21(cip1) by the viral protein NS1 arrests cells in G(2) through inhibition of cyclin A-dependent kinase activity.


Subject(s)
Cell Cycle , Cyclins/physiology , Minute Virus of Mice/physiology , Tumor Suppressor Protein p53/physiology , Viral Nonstructural Proteins/physiology , Animals , CDC2 Protein Kinase/physiology , Cell Line , Cyclin A/physiology , Cyclin-Dependent Kinase Inhibitor p21 , DNA Replication , G2 Phase , Rats , S Phase
4.
Exp Cell Res ; 250(2): 339-50, 1999 Aug 01.
Article in English | MEDLINE | ID: mdl-10413588

ABSTRACT

We have studied the response of human transformed cells to mitotic spindle inhibition. Two paired cell lines, K562 and its parvovirus-resistant KS derivative clone, respectively nonexpressing and expressing p53, were continuously exposed to nocodazole. Apoptotic cells were observed in both lines, indicating that mitotic spindle impairment induced p53-independent apoptosis. After a transient mitotic delay, both cell lines exited mitosis, as revealed by flow-cytometric determination of MPM2 antigen and cyclin B1 expression, coupled to cytogenetic analysis of sister centromere separation. Both cell lines exited mitosis without chromatid segregation. K562 p53-deficient cells further resumed DNA synthesis, giving rise to cells with a DNA content above 4C, and reentered a polyploid cycle. In contrast, KS cells underwent a subsequent G1 arrest in the tetraploid state. Thus, G1 arrest in tetraploid cells requires p53 function in the rereplication checkpoint which prevents the G1/S transition following aberrant mitosis; in contrast, p53 expression is dispensable for triggering the apoptotic response in the absence of mitotic spindle.


Subject(s)
Apoptosis , Cell Cycle Proteins , DNA Replication/genetics , Genes, p53 , Spindle Apparatus/physiology , Apoptosis/drug effects , Cell Cycle/drug effects , Centromere/drug effects , Centromere/metabolism , Chromosome Segregation/drug effects , Cyclin B/analysis , Cyclin B1 , DNA/biosynthesis , DNA Fragmentation/drug effects , DNA Replication/drug effects , Dose-Response Relationship, Drug , Flow Cytometry , Humans , Kinesins , Mitotic Index/drug effects , Nocodazole/pharmacology , Phosphoproteins/analysis , Polyploidy , Spindle Apparatus/drug effects , Tumor Cells, Cultured , Tumor Suppressor Protein p53/physiology
5.
J Virol ; 71(7): 5323-9, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9188601

ABSTRACT

The nonstructural protein NS1 of the autonomous parvovirus minute virus of mice interferes with cell division and can cause cell death, depending on the cell transformation state. Upon infection, the synthesis of NS1 protein is massively initiated during S phase. In this article, we show that minute virus of mice-infected cells accumulate in this phase. To investigate the link between NS1 accumulation and S-phase arrest, we have used stably transfected cells in which NS1 expression is under the control of a glucocorticoid-inducible promoter (the long terminal repeat of mouse mammary tumor virus). NS1 expression interferes with cell DNA replication, and consequently, the cell cycle stops in S phase. NS1 expression also induces nicks in the cell chromatin, as detected by an in situ nick translation assay. The nicks are observed several hours before any cell cycle perturbation. As cell cycle arrest is a common consequence of DNA damage, we propose that NS1 exerts its cytostatic activity by inducing lesions in cell chromatin.


Subject(s)
Chromatin , DNA Replication , Nucleic Acid Synthesis Inhibitors/metabolism , Viral Nonstructural Proteins/metabolism , Animals , Cell Line, Transformed , Humans , Mice , Minute Virus of Mice/physiology , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , S Phase , Viral Nonstructural Proteins/genetics
6.
J Virol ; 71(6): 4671-8, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9151861

ABSTRACT

Autonomous parvoviruses exert lytic and cytostatic effects believed to contribute to their antineoplastic activity. Studies with inducible clones have demonstrated a direct involvement of parvovirus nonstructural proteins (NS) in oncolysis. Human and rat fibroblasts have been stably transfected with MVM(p) (minute virus of mice prototype strain) NS genes cloned under the control of a hormone-inducible promoter. Dexamethasone-induced synthesis of the NS proteins in sensitive transformed cells results in cell killing within a few days. From these sensitive cell lines have been isolated some NS-resistant clones that also prove resistant to MVM(p) infection, suggesting that cell factors modulate NS cytotoxicity. We have previously reported that factors involved in cell cycle regulation may contribute to this modulation, since NS toxicity requires cell proliferation and correlates with a cell cycle perturbation leading to an arrest in phase S/G2. In addition to its role in cytotoxicity, NS1 can regulate transcription driven by parvovirus and nonparvovirus promoters. Since phosphorylation is a critical event in controlling the activity of many proteins, notably transcription factors and cell cycle-regulated proteins, we have examined the effect of NS1 on the synthesis and phosphorylation of cell proteins. Our results indicate that NS1 interferes, within 7 h of induction, with phosphorylation of a protein of about 14 kDa (p14). Cell synchronization has enabled us to show that phosphorylation of this protein occurs in early S phase and is prevented when NS1 is induced. This early effect of NS1 on p14 phosphorylation may be directly linked to cytotoxicity and is probably related to the previously reported inhibition of cell DNA synthesis. Late in the induction period (24 h), NS1 also alters the synthesis of a 50-kDa protein and a 35-kDa protein (p50 and p35, respectively). Microsequencing of p35 reveals sequence homology with beta-tubulin. These effects of NS1, observed only in NS1-sensitive cell lines, may be related to the protein's cytotoxicity.


Subject(s)
Gene Expression Regulation, Viral , Minute Virus of Mice/physiology , Phosphoproteins/metabolism , Viral Nonstructural Proteins/toxicity , Amino Acid Sequence , Animals , Cell Cycle/drug effects , Cell Survival/drug effects , Dexamethasone/pharmacology , Electrophoresis, Gel, Two-Dimensional , Gene Expression Regulation, Viral/drug effects , Isoelectric Point , Lovastatin/pharmacology , Mevalonic Acid/pharmacology , Molecular Sequence Data , Molecular Weight , Phosphoproteins/chemistry , Rats , S Phase , Tubulin/metabolism
7.
Prog Cell Cycle Res ; 3: 1-19, 1997.
Article in English | MEDLINE | ID: mdl-9552402

ABSTRACT

Viruses depend on the host's machineries to replicate and express their genome. Actively replicating cells have large pools of deoxynucleotides and high levels of key enzyme activities that viruses exploit to their own needs. Some viruses have developed strategies for driving quiescent cells into the S phase of the cell cycle, e.g. adenovirus, others, such as parvovirus, wait until the host itself begins to replicate. Viruses may also force the host cell to stay in a favourable phase, e.g. Epstein-Barr virus, or, if necessary, they may inhibit apoptotic cell death, e.g. human cytomegalovirus. In this review, we focus on the different strategies that viruses use to create in infected cells an environment favourable to the accomplishment of the viral life cycle through acting on cell cycle regulators.


Subject(s)
Cell Cycle/physiology , Virus Physiological Phenomena , Viruses/pathogenicity , Animals , G1 Phase/physiology , Humans , Models, Biological , S Phase/physiology , Viral Proteins/physiology , Virus Diseases/pathology , Virus Diseases/physiopathology , Virus Diseases/virology , Virus Replication/physiology , Viruses/growth & development
8.
Cell Growth Differ ; 6(7): 781-7, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7547499

ABSTRACT

The nonstructural (NS) proteins of the autonomous parvovirus minute virus of mice (prototype strain) are involved in viral DNA replication and in the regulation of parvoviral and heterologous promoters. By constructing cell lines having integrated the NS coding sequence under the control of an inducible promoter, we were able to demonstrate that NS proteins are toxic, once expressed in the transformed cells. Cell killing appears after several days of NS expression, suggesting that NS toxicity involved cellular factors. In this paper, we show that NS proteins are cytotoxic and interfere with the cell cycle in proliferating cells only NS expression is innocuous in resting cells, whereas in growing cells, it induces the accumulation of G2 cells. This cytostatic effect is enhanced upon neoplastic transformation, which sensitized the cells to NS killing. Moreover, as clones resistant to NS toxicity undergo no alteration of their cycle, this cytostatic effect of NS proteins could be an early step on the way to cell killing. These observations strongly suggest that NS toxicity involves cellular factors associated with the regulation of the cell cycle.


Subject(s)
Cell Cycle/physiology , G2 Phase/physiology , Minute Virus of Mice/physiology , Viral Nonstructural Proteins/toxicity , Animals , Cell Division/physiology , Cell Line, Transformed/cytology , Cell Line, Transformed/virology , Fibroblasts/virology , Flow Cytometry , Fluorescent Dyes , Gene Expression/physiology , Humans , Kidney/cytology , Minute Virus of Mice/chemistry , Minute Virus of Mice/genetics , Rats , Rats, Inbred F344
9.
J Virol ; 68(10): 6446-53, 1994 Oct.
Article in English | MEDLINE | ID: mdl-8083981

ABSTRACT

The nonstructural (NS) proteins of the autonomous parvovirus minute virus of mice are involved in viral DNA replication and in the regulation of homologous and heterologous promoters. Moreover, NS products have proved to be cytotoxic, especially for transformed cells. We show here that intracellular accumulation of NS products is not sufficient to kill rat fibroblasts from the established cell line FR3T3, which is phenotypically normal in several respects. FRNS cell lines were obtained by stable transfection of FR3T3 cells by a vector carrying the NS genes under the control of the hormone-inducible long terminal repeat promoter of the mouse mammary tumor virus. In the presence of dexamethasone, the NS proteins were synthesized without associated cell death. Transformation of FRNS cells with the c-Ha-ras oncogene or polyomavirus oncogenes had little effect on their capacity for NS induction, as measured at both concentration and transactivating activity levels, yet the transformants were now dying within a few days in the presence of the inducer. The same results were obtained with cells stably transfected by a vector expressing the NS1 product alone, suggesting that in this system there is no cooperation between NS1 and NS2 for maximal cytopathic effect. Cell mortality after NS protein induction was quantitatively related to the yield of oncogene expression, while NS-1 was not limiting in this respect. Our results show that the NS1 protein is not lethal unless cellular factors that may depend on oncogene expression trigger its cytotoxicity.


Subject(s)
Cell Survival , Gene Expression , Genes, ras , Minute Virus of Mice/genetics , Minute Virus of Mice/pathogenicity , Proto-Oncogene Proteins p21(ras)/biosynthesis , Viral Nonstructural Proteins/biosynthesis , Animals , Antigens, Polyomavirus Transforming/biosynthesis , Cell Division/drug effects , Cell Line , Cell Line, Transformed , Cell Survival/drug effects , Chloramphenicol O-Acetyltransferase/biosynthesis , Dexamethasone/pharmacology , Humans , Infant, Newborn , Kidney , Kinetics , Minute Virus of Mice/metabolism , Proto-Oncogene Proteins p21(ras)/analysis , Rats , Simian virus 40/genetics , Simian virus 40/metabolism , Transcriptional Activation , Transfection , Tumor Cells, Cultured , Urinary Bladder Neoplasms , Viral Nonstructural Proteins/analysis
10.
Virology ; 195(1): 149-55, 1993 Jul.
Article in English | MEDLINE | ID: mdl-8317090

ABSTRACT

The parvovirus-encoded nonstructural (NS) proteins have been implicated in the cytopathogenicity of these agents. Although protein NS-1 of minute virus of mice (MVM) has been shown to be toxic, little is known about the role of NS-2 in this process. In order to determine the contribution of NS-1 and NS-2 to cytotoxicity, we took advantage of an expression system controlled by the mouse mammary tumor virus promoter which responds to glucocorticoid stimulation and which controls the expression of both MVM(p) NS proteins. Different mutations were introduced in NS genes so as to affect the NS-1 or NS-2 protein. Neoplastic human cell lines expressing only NS-1 protein after induction by dexamethasone undergo a smaller lethality compared to lines expressing both wild-type proteins. Mutations that were introduced in NS-1 coding sequence and did not affect NS-2 were found to drastically suppress the cytotoxic effect. It is concluded that the NS-2 protein has little cytotoxic activity by itself but is required for the full expression of the viral cytopathic effect on transformed human cells. Furthermore these results lead us to suggest that the NS-2 cytotoxic domain is localized in the amino-terminal portion of the protein.


Subject(s)
Minute Virus of Mice/pathogenicity , Viral Nonstructural Proteins/biosynthesis , Base Sequence , Cell Division , Cell Line, Transformed , Cell Survival , Cloning, Molecular , Cytopathogenic Effect, Viral , DNA, Viral , Dexamethasone , Humans , Immunoblotting , Minute Virus of Mice/metabolism , Molecular Sequence Data , Mutagenesis, Site-Directed , Plasmids , Promoter Regions, Genetic , Viral Nonstructural Proteins/toxicity
11.
EMBO J ; 9(9): 2989-95, 1990 Sep.
Article in English | MEDLINE | ID: mdl-2167840

ABSTRACT

Although its dependence on the target cell type is well established, the cytopathogenicity of parvoviruses has remained elusive to date as far as its mechanism is concerned. However, indirect evidence suggested that parvoviral non-structural (NS) proteins may be the cytotoxic effectors. In order to test this hypothesis, a molecular clone of parvovirus MVMp was modified, by replacing the P4 promoter of the NS transcription unit by the glucocorticoid-inducible promoter of the mouse mammary tumour virus. Clones of neoplastic human cells that had incorporated this construct and that were induced to produce NS proteins by dexamethasone, showed a cytopathic effect and eventually died. Our data strongly suggest that the intracellular accumulation of parvoviral NS products jeopardizes the survival of the cells, which cannot be detected unless a threshold protein concentration is reached. Interestingly, a cell variant could be isolated which resisted dexamethasone-induced killing, although it was fully inducible for the production of NS proteins. This variant was also unusually resistant to infection with MVMp virions, thus confirming the essential role played by the NS proteins in the parvoviral cytotoxicity and indicating that the cytocidal activity of the parvoviral NS products is modulated by cellular factors that may vary from one cell to another.


Subject(s)
Capsid/genetics , Cell Survival , Genes, Viral , Parvoviridae/genetics , Viral Core Proteins/genetics , Viral Structural Proteins/genetics , Capsid/metabolism , Cell Division , Cell Line , Cell Transformation, Viral , Clone Cells , Humans , Plasmids , Promoter Regions, Genetic , Restriction Mapping , Simian virus 40/genetics , Transfection , Viral Core Proteins/metabolism , Viral Nonstructural Proteins
12.
Mutat Res ; 230(2): 241-54, 1990 Jun.
Article in English | MEDLINE | ID: mdl-2165215

ABSTRACT

The SOS hypothesis postulated that the mutator effect on undamaged DNA that generates phage-untargeted mutagenesis (UTM) results directly from the mechanism of targeted mutagenesis. RecA protein, which stimulates the cleavage of both the LexA repressor and UmuD protein, and the UmuDC gene products are required for UV-induced targeted mutagenesis. The use of phage lambda for analyzing UV-induced mutagenesis has permitted a distinction to be made between the mechanisms of targeted and untargeted mutagenesis, in that the two processes differ with respect to their genetic requirements for recA+ and umuDC+ genes. In this paper, we show that (i) proficiency for excision repair is required for UTM in double-stranded DNA phage but not in single-stranded DNA phage; (ii) the umuC function, which is not required for UTM of the double-stranded DNA phage lambda, is necessary for untargeted mutagenesis of the single-stranded DNA phages M13 and phi X174; (iii) for both single-stranded and double-stranded DNA phage, UV irradiation of the host increases the level of recA730-induced UTM. Our results are also consistent with the interpretation that the expression of untargeted mutagenesis in phage lambda and in M13 depends on the polymerase and to a lesser extent on the exonuclease 5'----3', activities of PolI. These results suggest that the involvement of the RecA and UmuDC proteins may be related to more than the presence of base damage in the DNA substrate.


Subject(s)
Bacteriophages/genetics , DNA Repair , Mutation , SOS Response, Genetics , Bacterial Proteins/genetics , Bacteriophage lambda/genetics , Bacteriophage phi X 174/genetics , DNA Polymerase I/metabolism , DNA, Single-Stranded/genetics , DNA, Single-Stranded/radiation effects , DNA, Viral/genetics , DNA, Viral/radiation effects , Dose-Response Relationship, Radiation , Exonucleases/metabolism , Genes, Viral , Rec A Recombinases/genetics , Ultraviolet Rays
13.
Mol Gen Genet ; 213(2-3): 491-8, 1988 Aug.
Article in English | MEDLINE | ID: mdl-2972909

ABSTRACT

In Escherichia coli, induction of the SOS functions by UV irradiation or by mutation in the recA gene promotes an SOS mutator activity which generates mutations in undamaged DNA. Activation of RecA protein by the recA730 mutation increases the level of spontaneous mutation in the bacterial DNA. The number of recA730-induced mutations is greatly increased in mismatch repair deficient strains in which replication errors are not corrected. This suggests that the majority of recA730-induced mutations (90%) arise through correctable, i.e. non-targeted, replication errors. This recA730 mutator effect is suppressed by a mutation in the umuC gene. We also found that dam recA730 double mutants are unstable, segregating clones that have lost the dam or the recA mutations or that have acquired a new mutation, probably in one of the genes involved in mismatch repair. We suggest that the genetic instability of the dam recA730 mutants is provoked by the high level of replication errors induced by the recA730 mutation, generating killing by coincident mismatch repair on the two unmethylated DNA strands. The recA730 mutation increases spontaneous mutagenesis of phage lambda poorly. UV irradiation of recA730 host bacteria increases phage untargeted mutagenesis to the level observed in UV-irradiated recA+ strains. This UV-induced mutator effect in recA730 mutants is not suppressed by a umuC mutation. Therefore UV and the recA730 mutation seem to induce different SOS mutator activities, both generating untargeted mutations.


Subject(s)
DNA Repair , Escherichia coli/genetics , Genes, Bacterial , SOS Response, Genetics , Bacteriophage lambda/genetics , Bacteriophage lambda/radiation effects , DNA Damage , DNA Repair/radiation effects , Escherichia coli/radiation effects , Mutation , Rec A Recombinases/genetics , SOS Response, Genetics/radiation effects , Ultraviolet Rays
14.
J Mol Biol ; 177(1): 181-7, 1984 Jul 25.
Article in English | MEDLINE | ID: mdl-6235376

ABSTRACT

Mutagenesis of phage lambda towards clear-plaque phenotype (c+----c) results in two classes of mutants that can be distinguished genetically and morphologically. Indirect mutagenesis, i.e. mutagenesis of unirradiated phage lambda c+ stimulated by the ultraviolet irradiation of the Escherichia coli host, results in mixed bursts (c/c+) of turbid wild-type and clear-plaque mutant phages. Pure bursts of lambda c mutants are induced by irradiation of the phage genome. Irradiation of both phages and host bacteria stimulates the production of the two classes of mutant clones. We show that three different mutant alleles of the E. coli umuC gene only prevent the appearance of pure bursts of clear-plaque mutants, while mixed bursts are produced at least as frequently in umuC mutants as in the umuC+ parent.


Subject(s)
Bacteriophage lambda/genetics , Mutation , Ultraviolet Rays , Bacteriophage lambda/radiation effects
15.
EMBO J ; 3(4): 707-12, 1984 Apr.
Article in English | MEDLINE | ID: mdl-6233141

ABSTRACT

We have used bacteriophage lambda to characterize the mutator effect of the SOS response induced by u.v. irradiation of Escherichia coli. Mutagenesis of unirradiated phages grown in irradiated or unirradiated bacteria was detected by measuring forward mutagenesis in the immunity genes or reversion mutagenesis of an amber codon in the R gene. Relative to the wild-type, the SOS mutator effect was higher in E. coli mismatch correction-deficient mutants (mutH, mutL and mutS) and lower in an adenine methylation-deficient mutant ( dam3 ). We conclude that a large proportion of SOS-induced 'untargeted' mutations are removed by the methyl-directed mismatch correction system, which acts on newly synthesized DNA strands. The lower SOS mutator effect observed in E. coli dam mutants may be due to a selective killing of mismatch-bearing chromosomes resulting from undirected mismatch repair. The SOS mutator effect on undamaged lambda DNA, induced by u.v. irradiation of the host, appears to result from decreased fidelity of DNA synthesis.


Subject(s)
Escherichia coli/genetics , Mutation , Adenine/metabolism , Bacteriophage lambda/genetics , DNA Repair , DNA Replication , DNA, Bacterial/genetics , DNA, Bacterial/radiation effects , DNA, Viral/genetics , Escherichia coli/radiation effects , Methylation , Ultraviolet Rays
18.
Biochimie ; 64(8-9): 559-64, 1982.
Article in English | MEDLINE | ID: mdl-6814501

ABSTRACT

Regulation of genetic stability is discussed in terms of interactions between constitutive and inducible DNA repair processes with specific emphasis on the results of our experimental studies of mismatch correction and SOS induction in Escherichia coli.


Subject(s)
DNA Repair , Escherichia coli/genetics , Genes, Bacterial , Base Composition , DNA Replication , DNA, Bacterial/genetics , DNA-Directed DNA Polymerase/metabolism , Mutation
19.
C R Seances Soc Biol Fil ; 176(3): 406-10, 1982.
Article in French | MEDLINE | ID: mdl-6215107

ABSTRACT

The survival of ultraviolet light (UV)--irradiated lambda phage is increased when host bacteria are grown in the presence of the base analogue 2-amino-purine (2 AP) prior infection. This increase in survival, which we call "2-AP-reactivation", has the following characteristics: (1) it is not accompanied by mutagenesis; (2) it occurs in recA- and lexA- bacterial mutants; (3) is abolished in the polA- mutant (deficient in DNA polymerase I).


Subject(s)
2-Aminopurine/pharmacology , Adenine/analogs & derivatives , Bacteriophage lambda/radiation effects , DNA Repair/radiation effects , DNA, Viral/radiation effects , Escherichia coli/enzymology , DNA Polymerase I/physiology , Mutation/drug effects , Ultraviolet Rays
20.
Mol Gen Genet ; 188(1): 143-8, 1982.
Article in English | MEDLINE | ID: mdl-6217402

ABSTRACT

The survival of UV-irradiated lambda phages is increased when host bacteria are grown in the presence of the base analogue 2-aminopurine (2AP) before infection. This increase in survival, which we have called "2AP-reactivation" depends upon the concentration of 2AP and the time of exposure to 2AP. 2AP-reactivation can be distinguished from Weigle-reactivation in that it is not accompanied by an increase in mutagenesis, does not act on the single-stranded DNA bacteriophage phi X174, and occurs in recA and lexA bacteria. 2AP reactivation does not appear to involve known systems of recombinational repair, as it occurs in recB and recF bacteria, or excision repair, as it occurs in uvrA and uvrB bacteria. It is however dependent upon DNA polymerase I.


Subject(s)
2-Aminopurine/pharmacology , Adenine/analogs & derivatives , Bacteriophage lambda/genetics , DNA Repair/drug effects , Escherichia coli/genetics , Bacteriophage phi X 174 , DNA , DNA, Single-Stranded/radiation effects , DNA, Viral/radiation effects , Recombination, Genetic , Ultraviolet Rays , Virus Activation
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