PubMed Health⌕ Search

Biomedical subjects

F Delbos

Publications and source records attributed to F Delbos.

At least 19 recordsLinked to original sources
PubMed2001

Transcription, beta-like DNA polymerases and hypermutation.

This paper discusses two aspects of immunoglobulin (Ig) gene hypermutation. In the first approach, a transcription termination signal is introduced in an Ig light chain transgene acting as a mutation substrate, and transgenic lines are generated with control and mutant transgenes integrated in tandem. Analysis of transcription levels and mutation frequencies between mutant and control transgenes clearly dissociates transcription elongation and mutation, and therefore argues against models whereby specific pausing of the RNA polymerase during V gene transcription would trigger an error-prone repair process. The second part reports the identification of two novel beta-like DNA polymerases named Pol lambda and Pol mu, one of which (Pol mu) represents a good candidate for the Ig mutase due to its higher lymphoid expression and its similarity with the lymphoid enzyme terminal deoxynucleotidyl transferase. Peculiar features of the expression of this gene, including an unusual splicing variability and a splicing inhibition in response to DNA-damaging agents, are discussed.

Animals↗
PubMed2000

Two novel human and mouse DNA polymerases of the polX family.

We describe here two novel mouse and human DNA polymerases: one (pol lambda) has homology with DNA polymerase beta while the other one (pol mu) is closer to terminal deoxynucleotidyltransferase. However both have DNA polymerase activity in vitro and share similar structural organization, including a BRCT domain, helix-loop-helix DNA-binding motifs and polymerase X domain. mRNA expression of pol lambda is highest in testis and fetal liver, while expression of pol mu is more lymphoid, with highest expression both in thymus and tonsillar B cells. An unusually large number of splice variants is observed for the pol mu gene, most of which affect the polymerase domain. Expression of mRNA of both polymerases is down-regulated upon treatment by DNA damaging agents (UV light, gamma-rays or H(2)O(2)). This suggests that their biological function may differ from DNA translesion synthesis, for which several DNA polymerase activities have been recently described. Possible functions are discussed.

Alternative Splicing↗
PubMed1998

Mismatch repair deficiency interferes with the accumulation of mutations in chronically stimulated B cells and not with the hypermutation process.

Primary responses to the hapten phenyloxazolone and chronic responses to environmental antigens occurring in Peyer's patches were analyzed in two different mismatch repair-deficient backgrounds. Paradoxically, whereas primary responses were found normal in MSH2- and only slightly diminished in PMS2-deficient mice, mutations in Peyer's patch B cells from both k.o. animals were reduced three times, the subset of Peyer's patch B cells with highly mutated sequences being specifically missing in the mismatch repair-deficient context. Strikingly, germinal center B cells from Peyer's patches of k.o. animals showed microsatellite instability at an unprecedented level. We thus propose that the amount of DNA damages generated prevents these cells from recycling in germinal centers and that mismatch repair deficiency is only the indirect cause of the lower mutation incidence observed.

Adenosine Triphosphatases↗
PubMed1998

Probing immunoglobulin gene hypermutation with microsatellites suggests a nonreplicative short patch DNA synthesis process.

As the rate of Ig gene hypermutation approximates the level of nucleotide discrimination of DNA polymerases (10(-3) to 10(-4)), a local inhibition of proofreading and mismatch repair during semiconservative replication could generate the mutations introduced by the process. To address this question, we have constructed transgenic mice that carry a hypermutation substrate containing a "polymerase slippage trap": an Ig gene with a mono or dinucleotide tract inserted in its V region. The low amount of slippage events as compared to the number of mutations, the absence of transient misalignment mutations at the border of the repeats, and the dissociation between the amount of frameshifts and mutations when the transgene is put on mismatch repair-deficient genetic backgrounds, suggest that Ig gene hypermutation occurs by an error-prone short patch DNA synthesis taking place outside global DNA replication.

Animals↗
PubMed1997

Molecular typing of Enterococcus faecalis strains resistant to high levels of gentamicin and isolated in Romania.

Sixteen Enterococcus faecalis strains resistant to high levels of gentamicin, 15 of which were isolated in the same year in a Romanian hospital, harboured conjugative gentamicin resistance (Gm(r)) plasmids ranging from 55 to 85 kilobases. On the basis of restriction enzyme and DNA-DNA hybridization profiles of these plasmids, as well as of chromosomal SmaI macrorestriction and Tn916 hybridization patterns, clonal relationship was established for seven strains whereas the other strains were considered to be independent. Nine and seven of the Gm(r) plasmids carried Tn4001-like and Tn4001-truncated structures, respectively; the latter structures were truncated in the right-hand flanking extremity of the element.

Chromosomes, Bacterial↗
PubMed1993

Diversity of chromosomal genetic elements and gene identification in antibiotic-resistant strains of Streptococcus pneumoniae and Streptococcus bovis.

Antibiotic-resistant Streptococcus pneumoniae (26 strains) and Streptococcus bovis (28 strains), devoid of R plasmids, were examined for DNA-DNA homology to Tn916 and Tn3701. Tn916-like structures were found in 17 S. pneumoniae and 21 S. bovis strains. Tn916-modified structures were present in 6 S. pneumoniae and 2 S. bovis strains. Two strains of each species carried elements having a Tn3701-like composite structure. All these elements were chromosome-borne. No chromosomal elements were detected in 1 S. pneumoniae and 3 S. bovis strains.

Chromosomes, Bacterial↗
PubMed1993

Study of heterogeneity of chloramphenicol acetyltransferase (CAT) genes in streptococci and enterococci by polymerase chain reaction: characterization of a new CAT determinant.

An assay based on the utilization of degenerate primers that enable enzymatic amplification of an internal fragment of cat genes known to be present in gram-positive cocci was developed to identify the genes encoding chloramphenicol resistance in streptococci and enterococci. The functionality of this system was illustrated by the detection of cat genes belonging to four different hydridization classes represented by the staphylococcal genes catpC221, catpC194, catpSCS7, and the clostridial gene catP, and by the characterization of a new streptococcal cat gene designated catS. A sequence related to the clostridial catQ gene, which was present in one streptococcal strain, was not detected by this assay. These results reveal that these six cat genes account for chromosomal-borne chloramphenicol resistance in 12 group A, B, and G streptococci tested. By contrast, only three of these six cat genes (catpC221, catpC194, and catpSCS7) were detected on the 10 enterococcal plasmids studied here that encode resistance to chloramphenicol.

Amino Acid Sequence↗
PubMed1990

Tn3702, a conjugative transposon in Enterococcus faecalis.

Enterococcus faecalis strain D434 was found to carry on its chromosome a determinant encoding tetracycline-minocycline resistance (Tcr-Mnr) and to harbor both an R plasmid and a cryptic conjugative plasmid, pIP1141. The determinant coding for Tcr-Mnr was located on a conjugative transposon, designated Tn3702. The transposition of Tn3702 on to both pIP1141 and the hemolysin plasmid pIP964 yielded different derivatives each of which contained an 18.5-kilobase insert. The structure of Tn3702 is similar to that of the conjugative transposon Tn916.

Conjugation, Genetic↗
PubMed1990

Does a tetracycline resistance determinant of class N exist?

pMV120 was reported to carry the tetracycline resistance (Tcr) determinant of class N. We obtained tetracycline-susceptible transconjugants harboring plasmids with restriction enzyme profiles indistinguishable from those of pMV120 isolated from tetracycline-resistant clones. We conclude that pMV120 is a cryptic plasmid and that class N of Tcr determinants does not exist.

Cloning, Molecular↗
PubMed1986

Use of penicillin-binding proteins for the identification of enterococci.

The results of 20 physiological and fermentation tests and examination of the penicillin-binding proteins (PBPs) of 85 enterococcal strains demonstrated that the genus Enterococcus could be divided into at least nine distinct species: E. faecalis, E. faecium, E. durans, E. hirae, E. avium, E. gallinarum, E. casseliflavus, E. malodoratus and E. mundtii. Each species had a specific pattern of at least five PBPs, with molecular masses in the range of about 40-130 kDa. The pattern of PBPs may be useful for identification purposes, since some strains with unusual fermentation characteristics were assigned to species by this technique.

Bacterial Proteins↗
PubMed1984

Viridans streptococci in infective endocarditis: species distribution and susceptibility to antibiotics.

A method for the speciation of viridans streptococci (non-groupable) is described. The major identification criteria are based on the reactions to a series of biochemical tests, including acid production in lactose, inulin, raffinose, mannitol and sorbitol, hydrolysis of arginine, esculin and Na hippurate, and production of polysaccharides in 5% sucrose media. A total of 450 strains was isolated from blood cultures, 183 of which were from confirmed cases of subacute endocarditis. The latter were identified as follows (%): Streptococcus sanguis I (25.7), S. mitis (19.7), S. sanguis II (19.7), S. mutans (17.5), S. milleri (12), S. morbillorium (3.2) and S. salivarius (2.2). Susceptibility to antibiotics was studied for 129 of these strains: 68% were susceptible to all drugs tested, 20% were resistant only to tetracycline, 4% only to penicillin (MIC = 0.5-4 micrograms ml-1) and 8% were multiply resistant (tetracycline, macrolides and related drugs, chloramphenicol, penicillin, high-level resistance to kanamycin and/or streptomycin [MIC = 1000-80.00 micrograms ml-1].

Anti-Bacterial Agents↗
PubMed1982

High-level aminoglycoside resistance in group A, B, G, D (Streptococcus bovis), and viridans streptococci.

Of 20 clinical isolates of group A, B, G, D (Streptococcus bovis), and viridans streptococci, 5 transferred their antibiotic resistance markers into streptococcal recipients at a low frequency (10(-4) to 10(-8)) in the apparent absence of extrachromosomal elements. All strains carried genetic markers for high-level resistance to streptomycin, kanamycin, neomycin, lividomycin A, and ribostamycin, as well as resistance to macrolides and related drugs, tetracycline, and chloramphenicol.

Aminoglycosides↗