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The effect of colony density on the dimorphic switch was determined in natural strains of Saccharomyces cerevisiae. In some strains invasiveness and pseudohyphal (PH) growth were highly sensitive to colony density; moreover, strains constitutively able to invade the substrate with PH formation positively influenced the invasiveness but not the PH growth of a different strain less prone to the dimorphic switch. [ABSTRACT FROM AUTHOR]

This paper shows some results obtained by assaying the genotoxic activity on procaryotic and eucaryotic cells of some water-soluble psoralen derivatives. In particular, six newly Synthesized derivatives of 5-methoxypsoralen (5-MOP) and of 8-methoxypsoralen (8-MOP) were tested; in previous studies they showed a strong anti-proliferative activity and a slight phototoxic effect; moreover, in view of a clinical use in the therapy of hyperproliferative skin diseases, these drugs should be less toxic than their parent compounds because of their good water solubility which could lead to a more efficient absorption and excretion. All the compounds tested here have shown genotoxic activity on both procaryotic and eucaryotic systems: however, on the procaryotic cells the water-soluble derivatives were less genotoxic than their respective parent compounds 5-MOP and 8-MOP. Quite different results were obtained on V79 Chinese hamster cells, showing that, in general, the 8-methoxy-derivatives are more mutagenic than the methoxy-ones, although the 5-MOP itself was shown to be highly genotoxic in this system. This fact confirms that a conclusive estimate of the genotoxic risk related to the use of new drugs cannot be drawn from the results obtained on a single biological system. [ABSTRACT FROM PUBLISHER]

The mutagenic activity of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC), has been studied in bacteria and Chinese hamster cells with and without metabolic activation by rat liver microsomes. DTIC was found to be highly mutagenic in the two systems. It is noteworthy that DTIC in the prokaryotic systems did not require metabolic activation to be effective. By comparing the mutagenic activity on bacteria of DTIC and of its monomethyl- and hydroxymethyl-derivatives (MIC and HMIC), it is evident that MIC and HMIC display a pattern of mutagenicity different from DTIC. It suggests that neither MIC nor HMIC are the direct responsible metabolites for the mutagenic activity of DTIC in bacteria. [ABSTRACT FROM PUBLISHER]

Abstract Background Mutagenesis induced in the yeast Saccharomyces cerevisiae by starvation for nutrilites is a well-documented phenomenon of an unknown mechanism. We have previously shown that the polymerase delta proofreading activity controls spontaneous mutagenesis in cells starved for histidine. To obtain further information, we compared the effect of adenine starvation on mutagenesis in wild-type cells and, in cells lacking the proofreading activity of polymerase delta (phenotype Exo-, mutation pol3-01). Results Ade+ revertants accumulated at a very high rate on adenine-free plates so that their frequency on day 16 after plating was 1.5 × 10-4 for wild-type and 1.0 × 10-2 for the Exo- strain. In the Exo- strain, all revertants arising under adenine starvation are suppressors of the original mutation, most possessed additional nutritional requirements, and 50% of them were temperature sensitive. Conclusions Adenine starvation is highly mutagenic in yeast. The deficiency in the polymerase delta proofreading activity in strains with the pol3-01 mutation leads to a further 66-fold increase of the rate of mutations. Our data suggest that adenine starvation induces genome-wide hyper-mutagenesis in the Exo- strain.

The hypotheses is forwarded that the introduction in the environment of high concentrations of phenols and other aromatic compounds (AC) is one, perhaps the main cause of the continuously rising trend of malignant melanoma (MM) incidence. Two, non-mutually exclusive, possibilities could explain how AC may induce MM: (1) AC may act as inhibitors or alternative substrates of tyrosinase, the enzyme synthesizing melanin, thus impairing the melanocyte photoprotection. (2) AC may impair, directly or indirectly, the activity or synthesis of the melanocorticotropin receptor (MC1R), which photoprotects melanocytes from the UV rays (UVR) by stimulating the DNA repair system. Particularly suspected are sunscreens, as they contain high concentrations of a large variety of AC, three of which are known to be tyrosinase inhibitors. AC that may interfere with tyrosinase are also present in a large variety of medicines used orally or as creams, and in many industrial products with which man is frequently in contact., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

In nature, micro organisms experience numerous environmental stresses and generally grow poorly most of the time. In the last two decades it has become evident that mutations arise not only in actively dividing cells but also in non-replicating or slowly replicating cells starved for nutrients. In yeast, precise base selection and proofreading by replicative DNA polymerases δ and ε keep starvation-associated mutagenesis (SAM) at basal levels. Less is known about the role of replicative DNA polymerase α (Pol α). Here we provide evidence that Pol α is involved in the control of SAM in yeast cells starved for adenine by participation in sporadic replication and/or DNA repair under these conditions.

The role of haplodiploidy in the evolution of eusocial insects and why in Hymenoptera males do not perform any work is presently unknown. We show here that within-colony conflict caused by the coexistence of individuals of the same caste expressing the same character in different ways can be fundamental in the evolution of social characters in species that have already reached the eusocial condition. Mosaic colonies, composed by individuals expressing either the wild-type or a mutant phenotype, inevitably occurs during the evolution of advantageous social traits in insects. We simulated the evolution of an advantageous social trait increasing colony fitness in haplodiploid and diplodiploid species considering all possible conditions, i.e. dominance/recessivity of the allele determining the new social character, sex of the castes, and influence of mosaicism on the colony fitness. When mosaicism lowered colony fitness below that of the colony homogeneous for the wild type allele, the fixation of an advantageous social character was possible only in haplodiploids with female castes. When mosaicism caused smaller reductions in colony fitness, reaching frequencies of 90% was much faster in haplodiploids with female castes and dominant mutations. Our results suggest that the evolution of social characters is easier in haplodiploid than in diplodiploid species, provided that workers are females.

Pan-American mitochondrial DNA (mtDNA) haplogroup C1 has been recently subdivided into three branches, two of which (C1b and C1c) are characterized by ages and geographical distributions that are indicative of an early arrival from Beringia with Paleo-Indians. In contrast, the estimated ages of C1d--the third subset of C1--looked too young to fit the above scenario. To define the origin of this enigmatic C1 branch, we completely sequenced 63 C1d mitochondrial genomes from a wide range of geographically diverse, mixed, and indigenous American populations. The revised phylogeny not only brings the age of C1d within the range of that of its two sister clades, but reveals that there were two C1d founder genomes for Paleo-Indians. Thus, the recognized maternal founding lineages of Native Americans are at least 15, indicating that the overall number of Beringian or Asian founder mitochondrial genomes will probably increase extensively when all Native American haplogroups reach the same level of phylogenetic and genomic resolution as obtained here for C1d.

We examined the role of Saccharomyces cerevisiae uracil DNA glycosylase in the suppression of mutagenesis in non-dividing, adenine-starved cells expressing human activation-induced deaminase (AID) gene. Our aim was to further understand the mechanisms preventing starvation-associated mutagenesis in yeast and to explore the consequences of AID gene expression in non-proliferating eukaryotic cells. Genetic control of starvation-induced mutagenesis in many aspects is similar to the control of spontaneous logarithmic phase mutagenesis. Low DNA polymerase fidelity, defects of mismatch repair or post-replication repair lead to the elevation of mutagenesis. Less is known about the role of uracil in DNA. In yeast, the UNG1 gene codes for a uracil DNA glycosylase, which removes uracil from DNA, thus preventing an accumulation of mutations. The UNG1 gene is constitutively expressed at low levels throughout the cell cycle and peaks in late G1/early S phase. We have shown that the wild-type UNG1 allele protects from AID-induced mutations in starved cells to the same extent as it does in logarithmic growth phase cells. This finding implies that the first step in uracil removal by base excision repair (BER) is similar in these two conditions and provides the first data for understanding the role of BER in starvation-associated mutagenesis.

The sequencing of entire human mitochondrial DNAs belonging to haplogroup U reveals that this clade arose shortly after the "out of Africa" exit and rapidly radiated into numerous regionally distinct subclades. Intriguingly, the Saami of Scandinavia and the Berbers of North Africa were found to share an extremely young branch, aged merely approximately 9,000 years. This unexpected finding not only confirms that the Franco-Cantabrian refuge area of southwestern Europe was the source of late-glacial expansions of hunter-gatherers that repopulated northern Europe after the Last Glacial Maximum but also reveals a direct maternal link between those European hunter-gatherer populations and the Berbers.

Background: Mutagenesis induced in the yeast Saccharomyces cerevisiae by starvation for nutrilites is a well-documented phenomenon of an unknown mechanism. We have previously shown that the polymerase delta proofreading activity controls spontaneous mutagenesis in cells starved for histidine. To obtain further information, we compared the effect of adenine starvation on mutagenesis in wild-type cells and, in cells lacking the proofreading activity of polymerase delta (phenotype Exo-, mutation pol3-01)., Results: Ade+ revertants accumulated at a very high rate on adenine-free plates so that their frequency on day 16 after plating was 1.5 x 10(-4) for wild-type and 1.0 x 10(-2) for the Exo- strain. In the Exo- strain, all revertants arising under adenine starvation are suppressors of the original mutation, most possessed additional nutritional requirements, and 50% of them were temperature sensitive., Conclusions: Adenine starvation is highly mutagenic in yeast. The deficiency in the polymerase delta proofreading activity in strains with the pol3-01 mutation leads to a further 66-fold increase of the rate of mutations. Our data suggest that adenine starvation induces genome-wide hyper-mutagenesis in the Exo- strain.

In this study we show that thermotolerance and thermoresistance of the yeast Saccharomyces cerevisae is enhanced when cells are in colonial condition. We also describe a method to select stable thermoresistant mutants which produce colonies from single plated cells at a temperature 2.5 degrees C higher than the maximum growth temperature of their parental strain.

The spontaneous and UV-induced frequencies of recessive mutations have been studied in a diploid strain of Aspergillus nidulans, by the p-fluoro-phenylalanine (FPA) and 8-azaguanine (8-AZA) resistance tests, on either resting or germinating conidia. Observed frequencies are in the order of magnitude of those expected, which have been calculated considering the observed mutation frequencies in the haploid strain as well as the mitotic recombination frequencies. We also review some papers which claim to have found higher rates of recessive mutations in mammalian cell lines; in some cases no really higher rates are evident and the authors' conclusions often rest on misinterpretation of their own data.

Four furocoumarins, two having a linear structure (psoralen and 8-methyl-psoralen) and two having an angular structure (angelicin and 4,5'-dimethyl-angelicin), were studied for their mutagenic activity in the HGPRT system on V79 chinese hamster cells in culture (V79/HGPRT system). All the four drugs, when activated by near-ultraviolet (NUV) light, were effective in inducing HGPRT mutants. Their efficiency ranked in the following order: 8-methyl-psoralen greater than psoralen = 4,5-dimethylangelicin greater than angelicin.

N and I group plasmids, which increase methylmethane sulfonate (MMS) mutagenesis in lexA+ strains of E. coli WP2 may be divided into two classes: those restoring part of the mutability of lexA- stains (class I) and those leaving lexA- strains non-mutable (class II). Almost complete restoration of MMS mutability is obtained by class I plasmids in a partially suppressed lexA rnm strain, while clase II plasmids cause far fewer MMS revertants in this strain than in lexA+. A pair of class I and II plasmids in lexA- shows a synergistic effect on mutability. These two classes do not coincide with plasmid division into incompatibility groups.

It has been suggested that conditions which lead to modifications in the chromatin structure could be responsible for an increased accessibility of DNA to genotoxic agents in eukaryotic cells. With this in mind, the cytotoxic and mutagenic activity of the anthracycline antibiotic, daunorubicin, and of UV radiation was assayed on V79 Chinese hamster cells pretreated or not with 5 mM sodium butyrate, an agent known to induce modifications in the chromatin structure: this treatment in fact proved to induce the hyperacetylation of the core histones, and moreover to enhance the cytotoxic response of the cells to both daunorubicin and UV radiation and the mutagenic response to daunorubicin.

The repair of methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) damages has been investigated in the fungus Aspergillus nidulans. 4 UV-sensitive mutants, namely uvsB, uvsD, uvsF and uvsH have been tested for their sensitivity and mutability to the above-mentioned agents. The results obtained show that: (1) uvsB and uvsD mutants are no more sensitive than the wild-type strain to the lethal action of EMS. In contrast, they are more sensitive to MMS; (2) uvsF and uvsH mutants are more sensitive than the wild type to EMS at 37 degrees C but not at 20 degrees C. However, they are more sensitive than the wild type to MMS at 37 degrees C as well as at 20 degrees C; (3) the mutation frequencies after treatment with either MMS or EMS plotted against survival are not altered in the UV-sensitive strains compared to the wild-type strain. From these data it may be concluded that the repair of lethal lesions induced by ethylating and methylating agents is under the control of different pathways. Furthermore the mutants tested are not involved in the mutagenic process.