Global mapping of DNA conformational flexibility on Saccharomyces cerevisiae.

In this study we provide the first comprehensive map of DNA conformational flexibility in Saccharomyces cerevisiae complete genome. Flexibility plays a key role in DNA supercoiling and DNA/protein binding, regulating DNA transcription, replication or repair. Specific interest in flexibility analysis concerns its relationship with human genome instability.

A top-down linguistic approach to the analysis of genomic sequences: The metabotropic glutamate receptors 1 and 5 in human and in mouse as a case study.

This paper presents a top-down strategy to detect features in genomic sequences. The strategy's core is to exploit dictionary-based compression algorithms and analyse the content of the automatically generated dictionary. We classify the different over-represented segments and in the case study we correlate them to experimentally identified or theoretically forecasted biological features.

Low-copy repeats on chromosome 22q11.2 show replication timing switches, DNA flexibility peaks and stress inducible asynchrony, sharing instability features with fragile sites.

The 22q11.2 region is a hotspot for chromosomal rearrangements mediated by LCR22A-D low-copy repeats. Sequence motifs and homology-driven mechanisms have been suggested to mediate rearrangements.

Correlated fragile site expression allows the identification of candidate fragile genes involved in immunity and associated with carcinogenesis.

Background: Common fragile sites (cfs) are specific regions in the human genome that are particularly prone to genomic instability under conditions of replicative stress. Several investigations support the view that common fragile sites play a role in carcinogenesis. We discuss a genome-wide approach based on graph theory and Gene Ontology vocabulary for the functional characterization of common fragile sites and for the identification of genes that contribute to tumour cell biology.

Chromosomal fragile sites FRA3B and FRA16D show correlated expression and association with failure of apoptosis in lymphocytes from patients with thyroid cancer.

It has been suggested that common fragile sites (cFSs) are related to cancer development. This appears to be the case for FRA3B and FRA16D, localized in two tumor-suppressor genes (FHIT and WWOX, respectively) that are altered by deletions or loss of heterozygosity (LOH) in many cancers. The features responsible for fragility have not yet been identified.

Endogenous sex hormones affect the mutagen-induced chromosome damage by altering a caffeine-sensitive checkpoint.

In the present study we analysed the effect of endogenous sex hormones on the SCE frequencies induced in vitro by mitomycin C (MMC), a bifunctional alkylating agent producing high chromosome damage and mitotic arrest. The analysis has been performed on lymphocytes obtained at three different phases of menstrual cycle, from women with regular cycle and hormones dosage. At all phases we further analysed the effect of a post-treatment with caffeine, an agent that it is known to overrride the DNA damage checkpoints.