Формування законодавчої і нормативної бази архівної справи в республіці Казахстан

Аналізується законодавство Республіки Казахстан, спрямоване на забезпечення збереження документальної спадщини, регулювання діяльності архівної системи в умовах державного суверенітету. Визначаються особливості архівного законодавства кінця 1990-х рр., прослідковуються його зміни та напрями удосконалення в 2000-х рр., процеси формування нормативної бази архівної справи.Анализируется законодательство Республики Казахстан, направленное на обеспечение сохранности документального наследия, регулирование деятельности архивной системы в условиях государственного суверенитета. Определяются особенности архивного законодательства конца 1990-х гг., прослеживаются его изменения и направления усовершенствования в 2000- х гг., процессы формирования нормативной базы архивного дела.The legislation of Republic of Kazakhstan, directed on providing of safety of documentary legacy, adjusting of activity of the archival system in the conditions of the state sovereignty is analysed in the article. The features of the archival legislation the end of 1990-th are determined, its changes and directions of improvement in the 2000-th, the processes of forming of normative base of the archival affairs are traced

Endoplasmic reticulum membrane contact sites : roles in phospholipid synthesis and cell polarity

Membrane contact sites between the endoplasmic reticulum (ER) and other organelles are present in all eukaryotic cells. Their roles in calcium signaling and transport between the ER and the plasma membrane (PM) or the ER and mitochondria are quite well understood, but the molecular mechanisms underlying their roles in lipid synthesis and transport remains unknown. In order to identify the importance of organelle-ER contact sites, I used Saccharomyces cerevisiae - a model organism that has proven to be a particularly informative for studying lipid-related cellular processes. Previously, we found a role for an ER anchor protein, Scs2, being important for PM-ER contact sites. Further, SCS2 interacts genetically with ICE2, an ER gene with unknown function. In Chapter 2, I investigated a role for PM–ER contact sites in regulating phosphatidylcholine (PC) synthesis and I found that Δscs2Δice2 cells are choline auxotrophs and PM–ER contacts are required for PC synthesis. Osh2 and Osh3, the oxysterol-binding protein homologues in yeast, rescued the choline auxotrophy phenotype of Δscs2Δice2 cells but did not restore pmaER, indicating that they may function with Opi3 in PC synthesis. In search for regulators of pmaER, we identified the phosphatidic acid phosphohydrolase Pah1 that seems to be involved in establishing pmaER, independent of its enzymatic activity. Finally, we proposed that PE to PC synthesis by Opi3 happens “in trans” at PM-ER contacts. In Chapter 3, I aimed to discover novel genes involved in PE synthesis/traffic from ER to mitochondria. By doing a genome-wide screen for CHO2, we identified genetic interactions between CHO2 and Emc proteins indicating that Emc proteins are important for PE metabolism and we proposed that Emc facilitates PS transfer from the ER to mitochondria for PE synthesis. In Chapter 4, I investigated for roles of SCS2 in polarized growth. I found a physiologically important function of the ER diffusion barrier, which is to restrict diffusion of the spindle from mother to bud until M phase. Scs2 interacts directly with the spindle capture protein Num1 and it prevents Num1 from diffusing from the mother into the bud during S and G2 phases.Medicine, Faculty ofGraduat

A Conserved Endoplasmic Reticulum Membrane Protein Complex (EMC) Facilitates Phospholipid Transfer from the ER to Mitochondria

<div><p>Mitochondrial membrane biogenesis and lipid metabolism require phospholipid transfer from the endoplasmic reticulum (ER) to mitochondria. Transfer is thought to occur at regions of close contact of these organelles and to be nonvesicular, but the mechanism is not known. Here we used a novel genetic screen in <i>S. cerevisiae</i> to identify mutants with defects in lipid exchange between the ER and mitochondria. We show that a strain missing multiple components of the conserved ER membrane protein complex (EMC) has decreased phosphatidylserine (PS) transfer from the ER to mitochondria. Mitochondria from this strain have significantly reduced levels of PS and its derivative phosphatidylethanolamine (PE). Cells lacking EMC proteins and the ER–mitochondria tethering complex called ERMES (the ER–mitochondria encounter structure) are inviable, suggesting that the EMC also functions as a tether. These defects are corrected by expression of an engineered ER–mitochondrial tethering protein that artificially tethers the ER to mitochondria. EMC mutants have a significant reduction in the amount of ER tethered to mitochondria even though ERMES remained intact in these mutants, suggesting that the EMC performs an additional tethering function to ERMES. We find that all Emc proteins interact with the mitochondrial translocase of the outer membrane (TOM) complex protein Tom5 and this interaction is important for PS transfer and cell growth, suggesting that the EMC forms a tether by associating with the TOM complex. Together, our findings support that the EMC tethers ER to mitochondria, which is required for phospholipid synthesis and cell growth.</p></div

Cells missing multiple EMC proteins have defects in PS transfer from the ER to mitochondria.

<p>(A) Cells with the indicated genotypes were labeled with [³H]serine for 30 min and the ratio of [³H]PS converted to [³H]PE determined (mean ±s.d., <i>n</i> = 3–5 independent experiments). The dashed red line indicates the amount of conversion that occurred in <i>psd1</i>Δ cells. * <i>p</i><0.05 compared to wild-type, independent two-tailed <i>t</i> test. (B) The 10-fold serial dilutions of cultures of the indicated strains were spotted onto SC medium with or without 5-FOA and ethanolamine. The plates were incubated at 30°C for 4 d. (C) PSD activity of crude mitochondria incubated with NBD-PS for 1 h at 30°C. PSD activity was normalized to that of wild-type crude-mitochondria (mean ±s.d., <i>n</i> = 2–3 independent experiments). * <i>p</i><0.05 compared to wild-type, independent two-tailed <i>t</i> test. The data used to generate panels A and C are in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001969#pbio.1001969.s010" target="_blank">Table S4</a>.</p

Genome-wide screen for regulators of phospholipid synthesis.

<p>(A) Phospholipid synthesis in the methylation pathway is compartmentalized between ER and mitochondria. PS synthesized in the ER is transferred to mitochondria for conversion into PE and transported back to the ER for conversion to PC. The Kennedy pathway synthesizes PE and PC from ethanolamine (etn) and choline (cho) independent of lipid transfer between ER and mitochondria. (B) Yeast growth assays for the indicated mutants in the absence (nil) or presence of ethanolamine (+ etn) or choline (+ cho). (C) Results of SGA screen for <i>CHO2</i> in the absence (–) and presence (+) of choline. Genetic interactions are plotted as the log2 of the ratio of growth of single versus double mutants with <i>Δcho2</i> in the absence and presence of choline. Interactions rescued by choline (green triangles) predominately clustered on the x axis, whereas interactions not rescued (red squares) were present on the diagonal. (D) Enrichment of functional groups for the genes that showed interactions and were rescued by choline in (C). Fold enrichment represents the frequency of a given term in our dataset relative to the frequency of that term in the whole genome.</p