Meiosis I Kinase Regulators: Conserved Orchestrators of Reductional Chromosome Segregation.

Research over the last two decades has identified a group of meiosis-specific proteins, consisting of budding yeast Spo13, fission yeast Moa1, mouse MEIKIN, and Drosophila Mtrm, with essential functions in meiotic chromosome segregation. These proteins, which we call meiosis I kinase regulators (MOKIRs), mediate two major adaptations to the meiotic cell cycle to allow the generation of haploid gametes from diploid mother cells. Firstly, they promote the segregation of homologous chromosomes in meiosis I (reductional division) by ensuring that sister kinetochores face towards the same pole (mono-orientation). Secondly, they safeguard the timely separation of sister chromatids in meiosis II (equational division) by counteracting the premature removal of pericentromeric cohesin, and thus prevent the formation of aneuploid gametes. Although MOKIRs bear no obvious sequence similarity, they appear to play functionally conserved roles in regulating meiotic kinases. Here, the known functions of MOKIRs are reviewed and their possible mechanisms of action are discussed. Also see the video abstract here https://youtu.be/tLE9KL89bwk.

Structures of CENP-C cupin domains at regional centromeres reveal unique patterns of dimerization and recruitment functions for the inner pocket.

The successful assembly and regulation of the kinetochore are critical for the equal and accurate segregation of genetic material during the cell cycle. CENP-C (centromere protein C), a conserved inner kinetochore component, has been broadly characterized as a scaffolding protein and is required for the recruitment of multiple kinetochore proteins to the centromere. At its C terminus, CENP-C harbors a conserved cupin domain that has an established role in protein dimerization. Although the crystal structure of the Saccharomyces cerevisiae Mif2CENP-C cupin domain has been determined, centromeric organization and kinetochore composition vary greatly between S. cerevisiae (point centromere) and other eukaryotes (regional centromere). Therefore, whether the structural and functional role of the cupin domain is conserved throughout evolution requires investigation. Here, we report the crystal structures of the Schizosaccharomyces pombe and Drosophila melanogaster CENP-C cupin domains at 2.52 and 1.81 Å resolutions, respectively. Although the central jelly roll architecture is conserved among the three determined CENP-C cupin domain structures, the cupin domains from organisms with regional centromeres contain additional structural features that aid in dimerization. Moreover, we found that the S. pombe Cnp3CENP-C jelly roll fold harbors an inner binding pocket that is used to recruit the meiosis-specific protein Moa1. In summary, our results unveil the evolutionarily conserved and unique features of the CENP-C cupin domain and uncover the mechanism by which it functions as a recruitment factor.

Predictive ecotoxicity of MoA 1 of organic chemicals using in silico approaches.

Persistent organic products are compounds used for various purposes, such as personal care products, surfactants, colorants, industrial additives, food, pesticides and pharmaceuticals. These substances are constantly introduced into the environment and many of these pollutants are difficult to degrade. Toxic compounds classified as MoA 1 (Mode of Action 1) are low toxicity compounds that comprise nonreactive chemicals. In silico methods such as Quantitative Structure-Activity Relationships (QSARs) have been used to develop important models for prediction in several areas of science, as well as aquatic toxicity studies. The aim of the present study was to build a QSAR model-based set of theoretical Volsurf molecular descriptors using the fish acute toxicity values of compounds defined as MoA 1 to identify the molecular properties related to this mechanism. The selected Partial Least Squares (PLS) results based on the values of cross-validation coefficients of determination (Qcv2) show the following values: Qcv2 = 0.793, coefficient of determination (R2) = 0.823, explained variance in external prediction (Qext2) = 0.87. From the selected descriptors, not only the hydrophobicity is related to the toxicity as already mentioned in previously published studies but other physicochemical properties combined contribute to the activity of these compounds. The symmetric distribution of the hydrophobic moieties in the structure of the compounds as well as the shape, as branched chains, are important features that are related to the toxicity. This information from the model can be useful in predicting so as to minimize the toxicity of organic compounds.