The role of DNA polymerase alpha in the control of mutagenesis in Saccharomyces cerevisiae cells starved for nutrients.

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.

Synthetic aromatic compounds interfering with melanogenesis are responsible of the rising trend of malignant melanoma incidence.

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.

Mosaicism may explain the evolution of social characters in haplodiploid Hymenoptera with female workers.

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.

The initial peopling of the Americas: a growing number of founding mitochondrial genomes from Beringia.

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.

High rate of starvation-associated mutagenesis in Ung(-) yeast caused by the overproduction of human activation-induced deaminase.

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.

Saami and Berbers--an unexpected mitochondrial DNA link.

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.

The exceptionally high rate of spontaneous mutations in the polymerase delta proofreading exonuclease-deficient Saccharomyces cerevisiae strain starved for adenine.

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.

The influence of colonial organization on thermotolerance and thermoresistance in Saccharomyces cerevisiae.

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.