Biomedical subjects

Shay Ben-Aroya

Publications and source records attributed to Shay Ben-Aroya.

4 recordsLinked to original sources

PubMed2004

The compact chromatin structure of a Ty repeated sequence suppresses recombination hotspot activity in Saccharomyces cerevisiae.

Recombination between repeated DNA sequences can have drastic consequences on the integrity of the genome. Repeated sequences are abundant in most eukaryotes, yet the mechanism that prevents recombination between them is currently unknown. Ty elements, the main family of dispersed repeats in Saccharomyces cerevisiae, exhibit low levels of exchange. Other regions in the genome have relatively high rates of meiotic recombination (hotspots). We show that a Ty element adjacent to the HIS4 recombination hotspot substantially reduces its activity, eliminating local DSB formation. We demonstrate that the Ty has a closed (nuclease-insensitive) chromatin configuration that is also imposed on the flanking DNA sequences. The compact chromatin structure is determined by sequences at the N terminus of the Ty. Increased binding of the Rap1 protein to the hotspot restores both open chromatin conformation and DSB formation. The chromatin configuration of Ty elements precludes initiation of recombination, thus preventing potentially lethal exchanges between repeated sequences.

Alcohol Oxidoreductases↗

PubMed2003

ELG1, a yeast gene required for genome stability, forms a complex related to replication factor C.

Many overlapping surveillance and repair mechanisms operate in eukaryotic cells to ensure the stability of the genome. We have screened to isolate yeast mutants exhibiting increased levels of recombination between repeated sequences. Here we characterize one of these mutants, elg1. Strains lacking Elg1p exhibit elevated levels of recombination between homologous and nonhomologous chromosomes, as well as between sister chromatids and direct repeats. These strains also exhibit increased levels of chromosome loss. The Elg1 protein shares sequence homology with the large subunit of the clamp loader replication factor C (RFC) and with the product of two additional genes involved in checkpoint functions and genome maintenance: RAD24 and CTF18. Elg1p forms a complex with the Rfc2-5 subunits of RFC that is distinct from the previously described RFC-like complexes containing Rad24 and Ctf18. Genetic data indicate that the Elg1, Ctf18, and Rad24 RFC-like complexes work in three separate pathways important for maintaining the integrity of the genome and for coping with various genomic stresses.

Amino Acid Sequence↗

PubMed2003

Pitfalls of the synthetic lethality screen in Saccharomyces cerevisiae: an improved design.

The colony color assay in yeast enables the visual identification of plasmid-loss events. In combination with a plasmid-dependence assay, it is commonly used to identify synthetic interactions between functionally related genes. Frequently, the plasmid carries the ADE3 gene and mutants are recognized as red colonies that fail to produce sectors. In these assays, a high percentage of false-positives is obtained, most of which result from synthetic lethality with the ade3 mutation. Here, we study the nature of these mutants. We report that mutations in the HIP1 and SHM1 genes exhibit synthetic lethality with ade3 deletions. A similar interaction is found between the fur1 and ura3 mutations. Lethality in the absence of the mitochondrial Shm1 and the cytoplasmic Ade3 enzymes indicates that, under certain circumstances, these cellular compartments cooperate in carrying out essential metabolic processes. In addition, we report the identification of a truncated ADE3 allele with a unique coloration phenotype and show that it can be used to improve synthetic lethal screens.

Genes, Lethal↗

PubMed2002

Control of meiotic recombination initiation: a role for the environment?

Homologous recombination plays a central role during meiosis, ensuring the proper segregation of homologous chromosomes during the first meiotic division. In addition, meiotic recombination generates genetic variability upon which natural selection can act. The frequency of recombination is not evenly distributed throughout the genome: regions of high (hotspots) and low (coldspots) recombination can be found. Meiotic hotspots exhibit high levels of double-strand break formation and these breaks coincide with the upstream regions of genes. In many cases, binding of transcription factors has been shown to be required for hotspot activity. We review the current knowledge on the mechanisms that determine hotspot activity and propose a modified model to account for recent observations which show that recombination frequency at hotspots is sensitive to environmental conditions.

Chromatin↗