E3 ubiquitin ligase RNF2 protects polymerase ι from destabilization.

Human DNA polymerase ι (Polι) belongs to the Y-family of specialized DNA polymerases engaged in the DNA damage tolerance pathway of translesion DNA synthesis that is crucial to the maintenance of genome integrity. The extreme infidelity of Polι and the fact that both its up- and down-regulation correlate with various cancers indicate that Polι expression and access to the replication fork should be strictly controlled. Here, we identify RNF2, an E3 ubiquitin ligase, as a new interacting partner of Polι that is responsible for Polι stabilization in vivo.

A novel role for Mms2 in the control of spontaneous mutagenesis and Pol3 abundance.

Mms2 is a ubiquitin E2-variant protein with a very well-documented function in the tolerance pathway that protects both human and yeast cells from the lethal and mutagenic effects of DNA damage. Interestingly, a high expression level of human MMS2 is associated with poor survival prognosis in different cancer diseases. Here we have analyzed the physiological effects of Mms2 overproduction in yeast cells.

Fires, vegetation, and human-The history of critical transitions during the last 1000 years in Northeastern Mongolia.

Fires are natural phenomena that impact human behaviors, vegetation, and landscape functions. However, the long-term history of fire, especially in the permafrost marginal zone of Central Asia (Mongolia), is poorly understood. This paper presents the results of radiocarbon and short-lived radionuclides (Pb and Cs) dating, pollen, geochemical, charcoal, and statistical analyses (Kohonen's artificial neural network) of sediment core obtained from Northern Mongolia (the Khentii Mountains region).

Long-term changes in hazardous heat and cold stress in humans: multi-city study in Poland.

Significant changes in climate variables in the last decades resulted in changes of perceived climate conditions. However, there are only few studies discussing long-lasting changes in bioclimatic conditions. Thus, the purpose of this paper is to present the temporal and spatial distribution of hazardous heat and cold stress conditions in different regions of Poland.

Developmental delay with hypotrophy associated with homozygous functionally relevant REV3L variant.

REV3L encodes a catalytic subunit of DNA polymerase zeta (Pol zeta) which is essential for the tolerance of DNA damage by inducing translesion synthesis (TLS). So far, the only Mendelian disease associated with REV3L was Moebius syndrome (3 patients with dominant REV3L mutations causing monoallelic loss-of-function were reported). We describe a homozygous ultra-rare REV3L variant (T2753R) identified with whole exome sequencing in a child without Moebius syndrome but with developmental delay, hypotrophy, and dysmorphic features who was born to healthy parents (heterozygous carriers of the variant).

Influence of geographical factors on thermal stress in northern Carpathians.

While general features of mountain climate are well recognised, there is not many research regarded their bioclimatic differentiation. The aim of the present study is to answer the question how different geographical factors: elevation above sea level, physiographical type of area, climate continentality and location of area in relation to the main mountain ridge influence thermal stress in northern Carpathians. To analyse thermal stress in the region, daily meteorological data from 21 stations of national weather networks of Poland, Ukraine and Slovakia for the period 1986-2015 were used.

Regulation of the abundance of Y-family polymerases in the cell cycle of budding yeast in response to DNA damage.

Y-family DNA polymerases mediate DNA damage tolerance via translesion synthesis (TLS). Because of the intrinsically error-prone nature of these enzymes, their activities are regulated at several levels. Here, we demonstrate the common regulation of the cellular abundance of Y-family polymerases, polymerase eta (Pol eta), and Rev1, in response to DNA damage at various stages of the cell cycle.

Lack of G1/S control destabilizes the yeast genome via replication stress-induced DSBs and illegitimate recombination.

The protein Swi6 in is a cofactor in two complexes that regulate the transcription of the genes controlling the G1/S transition. It also ensures proper oxidative and cell wall stress responses. Previously, we found that Swi6 was crucial for the survival of genotoxic stress.

PCNA SUMOylation protects against PCNA polyubiquitination-mediated, Rad59-dependent, spontaneous, intrachromosomal gene conversion.

Homologous recombination is crucial in both the maintenance of genome stability and the generation of genetic diversity. Recently, multiple aspects of the recombination machinery functioning at arrested DNA replication forks have been established, yet the roles of diverse modifications of PCNA, the key platform organizing the replication complex, in intrachromosomal recombination have not been comprehensively elucidated. Here, we report how PCNA SUMOylation and/or polyubiquitination affects recombination between direct repeats in S.

The steady-state level and stability of TLS polymerase eta are cell cycle dependent in the yeast S. cerevisiae.

Polymerase eta (Pol eta) is a ubiquitous translesion DNA polymerase that is capable of bypassing UV-induced pyrimidine dimers in an error-free manner. However, this specialized polymerase is error prone when synthesizing through an undamaged DNA template. In Saccharomyces cerevisiae, both depletion and overproduction of Pol eta result in mutator phenotypes.

The roles of PCNA SUMOylation, Mms2-Ubc13 and Rad5 in translesion DNA synthesis in Saccharomyces cerevisiae.

Mms2, in concert with Ubc13 and Rad5, is responsible for polyubiquitination of replication processivity factor PCNA. This modification activates recombination-like DNA damage-avoidance mechanisms, which function in an error-free manner. Cells deprived of Mms2, Ubc13 or Rad5 exhibit mutator phenotypes as a result of the channelling of premutational DNA lesions to often error-prone translesion DNA synthesis (TLS).

Evaluation of the roles of Pol zeta and NHEJ in starvation-associated spontaneous mutagenesis in the yeast Saccharomyces cerevisiae.

The vast majority of microorganisms live under starvation-associated stress conditions that cause mutagenesis despite the limitation of DNA replication and cell division. In this study, we compared the roles of polymerase zeta (Pol zeta) and non-homologous DNA-end joining (NHEJ) in starvation-associated spontaneous base substitutions and frameshifts, using yeast mutants carrying deletions of REV3 (encoding the catalytic subunit of Pol zeta), YKU80 (encoding a protein involved in the initiation of NHEJ), or both genes. We found that approximately 50% of starvation-associated spontaneous frameshifts and 40% of base substitutions required NHEJ to occur.

The spectrum of spontaneous mutations caused by deficiency in proteasome maturase Ump1 in Saccharomyces cerevisiae.

Ump1 is responsible for maturation of the catalytic core of the 26S proteasome. Dysfunction of Ump1 causes an increase in the frequency of spontaneous mutations in Saccharomyces cerevisiae. In this study we analyze the spectrum of mutations occurring spontaneously in yeast deficient in Ump1 by use of the SUP4-o system.

Nucleotide-dependent interaction of Saccharomyces cerevisiae Hsp90 with the cochaperone proteins Sti1, Cpr6, and Sba1.

The ATP-dependent molecular chaperone Hsp90 and partner cochaperone proteins are required for the folding and activity of diverse cellular client proteins, including steroid hormone receptors and multiple oncogenic kinases. Hsp90 undergoes nucleotide-dependent conformational changes, but little is known about how these changes are coupled to client protein activation. In order to clarify how nucleotides affect Hsp90 interactions with cochaperone proteins, we monitored assembly of wild-type and mutant Hsp90 with Sti1, Sba1, and Cpr6 in Saccharomyces cerevisiae cell extracts.

Analysis of the spontaneous mutator phenotype associated with 20S proteasome deficiency in S. cerevisiae.

Besides its role as a major recycler of unfolded or otherwise damaged intracellular proteins, the 26S proteasome functions as a regulator of many vital cellular processes and is postulated as a target for antitumor drugs. It has previously been shown that dysfunction of the catalytic core of the 26S proteasome, the 20S proteasome, causes a moderate increase in the frequency of spontaneous mutations in yeast [A. Podlaska, J.

Comparative kinetics of azathioprine and metazathioprine mercaptolysis in presence of physiological thiols.

Kinetic parameters of mercaptolysis of azathioprine (AZA) and metazathioprine (MAZA) to 6-mercaptopurine in phosphate buffer, pH 7.4, under the influence of physiological thiols (glutathione and cysteine) at 25 degrees, 30 degrees and 37 degrees C were determined and compared. It comes out that the mercaptolysis of MAZA is significantly faster under the influence of both mentioned thiols if compared to that reaction of AZA.

The influence of the mismatch-repair system on stationary-phase mutagenesis in the yeast Saccharomyces cerevisiae.

Stationary-phase (also called adaptive) mutation occurs in non-dividing cells during prolonged non-lethal selective pressure, e.g. starvation for an essential amino acid.