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Biomedical subjects

M Belisle

Publications and source records attributed to M Belisle.

4 recordsLinked to original sources
PubMed1999

Intron homing with limited exon homology. Illegitimate double-strand-break repair in intron acquisition by phage t4.

The td intron of bacteriophage T4 encodes a DNA endonuclease that initiates intron homing to cognate intronless alleles by a double-strand-break (DSB) repair process. A genetic assay was developed to analyze the relationship between exon homology and homing efficiency. Because models predict exonucleolytic processing of the cleaved recipient leading to homologous strand invasion of the donor allele, the assay was performed in wild-type and exonuclease-deficient (rnh or dexA) phage. Efficient homing was supported by exon lengths of 50 bp or greater, whereas more limited exon lengths led to a precipitous decline in homing levels. However, extensive homology in one exon still supported elevated homing levels when the other exon was completely absent. Analysis of these "one-sided" events revealed recombination junctions at ectopic sites of microhomology and implicated nucleolytic degradation in illegitimate DSB repair in T4. Interestingly, homing efficiency with extremely limiting exon homology was greatly elevated in phage deficient in the 3'-5' exonuclease, DexA, suggesting that the length of 3' tails is a major determinant of the efficiency of DSB repair. Together, these results suggest that illegitimate DSB repair may provide a means by which introns can invade ectopic sites.

Bacteriophage T4↗
PubMed1995

Selection of a remote cleavage site by I-tevI, the td intron-encoded endonuclease.

I-TevI, a double-strand DNA endonuclease involved in the mobility of the td intron of phage T4, is highly unusual in that it binds and cleaves intronless td alleles (td homing sites) in a site-specific but sequence-tolerant manner. The endonuclease binds to sequences flanking the intron insertion site and near the remote cleavage site, located 23 and 25 nucleotides away on the top and bottom strands, respectively. Mapping studies indicate that I-TevI has both sequence and distance sensors that function during cut-site selection. Although I-TevI cleavage of many insertion and deletion variants of the homing site is impaired, double-strand breaks are generated at positions that collectively span two turns of the helix, indicating that the interaction is extraordinarily flexible. However, the endonuclease does exhibit spacing preferences between its binding domains, and sequence preferences near the cleavage site, with the G:C pair at -23 implicated as a cleavage determinant. Furthermore, I-TevI appears to function through interactions across the minor groove at the cleavage site, as it does at the intron insertion site, and to be capable of cleaving sequentially, first on the bottom and then on the top strand. These properties of I-TevI are incorporated in a model wherein the endonuclease effects distant cleavage via a flexible hinge.

Bacteriophage T4↗
PubMed1994

The treatment of avoidant personality disorder by social skills training in the clinic or in real-life settings.

Twenty-eight outpatients who met DSM-III diagnostic criteria for avoidant personality disorder completed 14 one and a half hour sessions of social skills training in the clinic only or a combination of four sessions in the clinic, four sessions in real-life and six follow-up sessions in the clinic. Subjects were assessed before treatment began, after four sessions, at the end of treatment and at three month follow-up points. Training in real-life did not enhance social skills training; no significant difference between the groups at any assessment points was found. In both groups improvement in time was significant and clinically worthwhile. The treatment effects were maintained up to the three month follow-up, where available. Social skills training appears to be a useful and promising intervention for avoidant personality disorder but its long term impact remains to be investigated.

Adolescent↗