Accumulation of single-stranded DNA and destabilization of telomeric repeats in yeast mutant strains carrying a deletion of RAD27.

The Saccharomyces cerevisiae RAD27 gene encodes the yeast homologue of the mammalian FEN-1 nuclease, a protein that is thought to be involved in the processing of Okazaki fragments during DNA lagging-strand synthesis. One of the predicted DNA lesions occurring in rad27 strains is the presence of single-stranded DNA of the template strand for lagging-strand synthesis. We examined this prediction by analyzing the terminal DNA structures generated during telomere replication in rad27 strains. The lengths of the telomeric repeat tracts were found to be destabilized in rad27 strains, indicating that naturally occurring direct repeats are subject to tract expansions and contractions in such strains. Furthermore, abnormally high levels of single-stranded DNA of the templating strand for lagging-strand synthesis were observed in rad27 cells. Overexpression of Dna2p in wild-type cells also yielded single-stranded DNA regions on telomeric DNA and caused a cell growth arrest phenotype virtually identical to that seen for rad27 cells grown at the restrictive temperature. Furthermore, overexpression of the yeast exonuclease Exo1p alleviated the growth arrest induced by both conditions, overexpression of Dna2p and incubation of rad27 cells at 37 degrees C. However, the telomere heterogeneity and the appearance of single-stranded DNA are not prevented by the overexpression of Exo1p in these strains, suggesting that this nuclease is not simply redundant with Rad27p. Our data thus provide in vivo evidence for the types of DNA lesions predicted to occur when lagging-strand synthesis is deficient and suggest that Dna2p and Rad27p collaborate in the processing of Okazaki fragments.

Cytological and functional aspects of telomere maintenance.

The fact that eukaryotic chromosomes are linear poses a special problem for their maintenance: the natural ends of chromosomes must be distinguished from ends generated by chromosomal breakage and somehow, the chromosome ends must also be fully replicated to maintain their integrity. Telomeres, the complex structures at the ends of chromosomes are thought to be instrumental for both of these functions. However, recent insights in telomere biology suggest that these terminal structures do much more than just fulfill these two basic functions. Cytological data demonstrate that telomeres may play leading roles in chromatin organization and nuclear architecture during mitosis and meiosis. Moreover, non-functional telomeres may lead to genetic instability, a common prelude to cancer. Here, we review the basic functions of telomeres during chromosome replication and discuss the cytological aspects of telomere function during mitosis and meiosis.

[The MRC (County Regional Municipality) team: new configuration of the team and mental health reform]. / Equipe MRC: nouvelle configuration des équipes de réinsertion en santé mentale.

The concept of the équipe MRC (county regional municipality team) has developed as a result of the rapid transformation of mental health services. In most regions of Quebec, there has been a transition from an institutional model, where all services were provided by a single establishment, to a dispersed model where there are a whole range of services provided by a multitude of agencies. In this context, partnership becomes a necessity. The intention of the équipe MRC is thus to provide a structure that brings together under the same aegis all the public-sector and community-based personnel working with clients who suffer from severe and persistent mental health problems. This article seeks to define the concept of the équipe MRC and to assess the state of collaboration among the members of these teams, taking into account the fact that relations between community-based and public-sector agencies have not always been productive.

The Regnault "B" technique in mastopexy and breast reduction: a 12-year review.

The "B" technique for mastopexy and reduction with and without prosthesis has been used by the author over the last 12 years for all forms of breast ptosis and hypertrophy. It has been used consistently and uniquely in over 1000 cases. Its cosmetic advantages are the short length of the scar, avoidance of a median projection of the scar, and a beautiful roundness in the best cases. The technique proved to be very adaptable to various deformities and is easy to use. The percent of complications is thought to be no greater than that of other techniques.