Synthetic lethality between toxic amino acids, RTG-target genes and chaperones in Saccharomyces cerevisiae.

The toxicity of non-proteinogenic amino acids has been known for decades. Numerous reports describe their antimicrobial/anticancer potential. However, these molecules are often toxic to the host as well; thus, a synthetic lethality approach that reduces the dose of these toxins while maintaining toxicity can be beneficial.

Dynamic responses of Fusarium mangiferae to ultra-violet radiation.

The repair capacity of ultra-violet (UV) light DNA damage is important for adaptation of fungi to different ecological niches. We previously showed that in the soil-borne pathogen Fusarium oxysporum photo-reactivation dependent UV repair is induced at the germling stage and reduced at the filament stage. Here, we tested the developmental control of the transcription of photolyase, UV survival, UV repair capacity, and UV induced mutagenesis in the foliar pathogen Fusarium mangiferae.

Genomic structural plasticity of rodent-associated Bartonella in nature.

Rodent-associated Bartonella species have shown a remarkable genetic diversity and pathogenic potential. To further explore the extent of the natural intraspecific genomic variation and its potential role as an evolutionary driver, we focused on a single genetically diverse Bartonella species, Bartonella krasnovii, which circulates among gerbils and their associated fleas. Twenty genomes from 16 different B.

Adaptive Resistance Mutations at Suprainhibitory Concentrations Independent of SOS Mutagenesis.

Emergence of resistant bacteria during antimicrobial treatment is one of the most critical and universal health threats. It is known that several stress-induced mutagenesis and heteroresistance mechanisms can enhance microbial adaptation to antibiotics. Here, we demonstrate that the pathogen Bartonella can undergo stress-induced mutagenesis despite the fact it lacks error-prone polymerases, the rpoS gene and functional UV-induced mutagenesis.

Genomic Instability in Fungal Plant Pathogens.

Fungi and fungal-like organisms (oomycetes) that cause diseases in plants have impacted human communities for centuries and probably from the dawn of agriculture. In modern agriculture, there is a constant race between new strategies to manage fungal plant pathogens and their ability to adapt. An important component in this race is fungal genetic diversity.

Developmentally Regulated Oscillations in the Expression of UV Repair Genes in a Soilborne Plant Pathogen Dictate UV Repair Efficiency and Survival.

The ability to withstand UV damage shapes the ecology of microbes. While mechanisms of UV tolerance were extensively investigated in microorganisms regularly exposed to the sun, far less is known about UV repair of soilborne microorganisms. is a soilborne fungal plant pathogen that is resistant to UV light.

Limited DNA Repair Gene Repertoire in Ascomycete Yeast Revealed by Comparative Genomics.

Ascomycota is the largest phylogenetic group of fungi that includes species important to human health and wellbeing. DNA repair is important for fungal survival and genome evolution. Here, we describe a detailed comparative genomic analysis of DNA repair genes in Ascomycota.

Ribonucleotide reductase from Fusarium oxysporum does not Respond to DNA replication stress.

Ribonucleotide reductase (RNR) catalyzes the rate limiting step in dNTP biosynthesis and is tightly regulated at the transcription and activity levels. One of the best characterized responses of yeast to DNA damage is up-regulation of RNR transcription and activity and consequently, elevation of the dNTP pools. Hydroxyurea is a universal inhibitor of RNR that causes S phase arrest.

Alternative Functional Paralogs in .

Cohesin, the sister chromatid cohesion complex, is an essential complex that ensures faithful sister chromatid segregation in eukaryotes. It also participates in DNA repair, transcription and maintenance of chromosome structure. Mitotic cohesin is composed of Smc1, Smc3, Scc3, and Rad21/Mcd1.

The response to the DNA damaging agent methyl methanesulfonate in a fungal plant pathogen.

DNA damage can cause mutations that in fungal plant pathogens lead to hypervirulence and resistance to pesticides. Almost nothing is known about the response of these fungi to DNA damage. We performed transcriptomic and phosphoproteomic analyses of Fusarium oxysporum exposed to methyl methanesulfonate (MMS).

The Goldilocks effect of respiration on canavanine tolerance in Saccharomyces cerevisiae.

When glucose is available, Saccharomyces cerevisiae prefers fermentation to respiration. In fact, it can live without respiration at all. Here, we study the role of respiration in stress tolerance in yeast.

How Does Sense and Respond to Nicotinaldehyde, an Inhibitor of the NAD Salvage Biosynthesis Pathway?

Plant pathogenic fungi are a major threat to food security and impose a severe economic burden, thus there is a continuous need to develop new strategies to manage them. NAD is a co-factor in numerous enzymatic activities and determines the metabolic fate of the cell. Therefore, maintenance of NAD concentration is important for cellular viability.

Untangling the knots: Co-infection and diversity of Bartonella from wild gerbils and their associated fleas.

Based on molecular data, previous studies have suggested a high overall diversity and co-infection rates of Bartonella bacteria in wild rodents and their fleas. However, partial genetic characterization of uncultured co-infecting bacteria limited sound conclusions concerning intra- and inter-specific diversity of the circulating Bartonella. To overcome this limitation, Bartonella infections of wild populations of two sympatric gerbil species and their fleas were explored by multiple isolations of Bartonella organisms.

Increased LOH due to Defective Sister Chromatid Cohesion Is due Primarily to Chromosomal Aneuploidy and not Recombination.

Loss of heterozygosity (LOH) is an important factor in cancer, pathogenic fungi, and adaptation to changing environments. The sister chromatid cohesion process (SCC) suppresses aneuploidy and therefore whole chromosome LOH. SCC is also important to channel recombinational repair to sister chromatids, thereby preventing LOH mediated by allelic recombination.

Whole Genome Sequence Analysis of Mutations Accumulated in Yeast Strains with Defects in the Processing of Okazaki Fragments Indicates Template-Switching Events.

Okazaki fragments that are formed during lagging strand DNA synthesis include an initiating primer consisting of both RNA and DNA. The RNA fragment must be removed before the fragments are joined. In , a key player in this process is the structure-specific flap endonuclease, Rad27p (human homolog FEN1).

Suppression of allelic recombination and aneuploidy by cohesin is independent of Chk1 in Saccharomyces cerevisiae.

Sister chromatid cohesion (SCC), which is established during DNA replication, ensures genome stability. Establishment of SCC is inhibited in G2. However, this inhibition is relived and SCC is established as a response to DNA damage, a process known as Damage Induced Cohesion (DIC).

The sister chromatid cohesion pathway suppresses multiple chromosome gain and chromosome amplification.

Gain or loss of chromosomes resulting in aneuploidy can be important factors in cancer and adaptive evolution. Although chromosome gain is a frequent event in eukaryotes, there is limited information on its genetic control. Here we measured the rates of chromosome gain in wild-type yeast and sister chromatid cohesion (SCC) compromised strains.

Characterization of constitutive CTCF/cohesin loci: a possible role in establishing topological domains in mammalian genomes.

Background: Recent studies suggested that human/mammalian genomes are divided into large, discrete domains that are units of chromosome organization. CTCF, a CCCTC binding factor, has a diverse role in genome regulation including transcriptional regulation, chromosome-boundary insulation, DNA replication, and chromatin packaging. It remains unclear whether a subset of CTCF binding sites plays a functional role in establishing/maintaining chromatin topological domains.

Understanding the origins of UV-induced recombination through manipulation of sister chromatid cohesion.

Ultraviolet light (UV) can provoke genome instability, partly through its ability to induce homologous recombination (HR). However, the mechanism(s) of UV-induced recombination is poorly understood. Although double-strand breaks (DSBs) have been invoked, there is little evidence for their generation by UV.

RAD53 is limiting in double-strand break repair and in protection against toxicity associated with ribonucleotide reductase inhibition.

The yeast Chk2/Chk1 homolog Rad53 is a central component of the DNA damage checkpoint system. While it controls genotoxic stress responses such as cell cycle arrest, replication fork stabilization and increase in dNTP pools, little is known about the consequences of reduced Rad53 levels on the various cellular endpoints or about its roles in dealing with chronic vs. acute genotoxic challenges.

Cohesin Is limiting for the suppression of DNA damage-induced recombination between homologous chromosomes.

Double-strand break (DSB) repair through homologous recombination (HR) is an evolutionarily conserved process that is generally error-free. The risk to genome stability posed by nonallelic recombination or loss-of-heterozygosity could be reduced by confining HR to sister chromatids, thereby preventing recombination between homologous chromosomes. Here we show that the sister chromatid cohesion complex (cohesin) is a limiting factor in the control of DSB repair and genome stability and that it suppresses DNA damage-induced interactions between homologues.

Translesion DNA synthesis-assisted non-homologous end-joining of complex double-strand breaks prevents loss of DNA sequences in mammalian cells.

Double strand breaks (DSB) are severe DNA lesions, and if not properly repaired, may lead to cell death or cancer. While there is considerable data on the repair of simple DSB (sDSB) by non-homologous end-joining (NHEJ), little is known about the repair of complex DSBs (cDSB), namely breaks with a nearby modification, which precludes ligation without prior processing. To study the mechanism of cDSB repair we developed a plasmid-based shuttle assay for the repair of a defined site-specific cDSB in cultured mammalian cells.

Numt-mediated double-strand break repair mitigates deletions during primate genome evolution.

Non-homologous end joining (NHEJ) is the major mechanism of double-strand break repair (DSBR) in mammalian cells. NHEJ has traditionally been inferred from experimental systems involving induced double strand breaks (DSBs). Whether or not the spectrum of repair events observed in experimental NHEJ reflects the repair of natural breaks by NHEJ during chromosomal evolution is an unresolved issue.