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Современные проблемы генетики и эволюция генома

Журнальные статьи

1.U12116
Chenais B. et al. The impact of transposable elements on eukaryotic genomes: From genome size increase to genetic adaptation to stressful environments // Gene. 2012. Vol. 509, № 1. P. 7–15.

Transposable elements (TEs) are present in roughly all genomes. These mobile DNA sequences are able to invade genomes and their impact on genome evolution is substantial. The mobility of TEs can induce the appearance of deleterious mutations, gene disruption and chromosome rearrangements, but transposition activity also has positive aspects and the mutational activities of TEs contribute to the genetic diversity of organisms. This short review aims to give a brief overview of the impact TEs may have on animal and plant genome structure and expression, and the relationship between TEs and the stress response of organisms, including insecticide resistance.

2.U15400
Dale J.L. et al. cis-Acting Elements That Control Expression of the Master Virulence Regulatory Gene atxA in Bacillus anthracis // J. Bacteriol. 2012. Vol. 194, № 15. P. 4069–4079.

Transcription of the Bacillus anthracis structural genes for the anthrax toxin proteins and biosynthetic operon for capsule is positively regulated by AtxA, a transcription regulator with unique properties. Consistent with the role of atxA in virulence factor expression, a B. anthracis atxA-null mutant is avirulent in a murine model for anthrax. In culture, multiple signals impact atxA transcript levels, and the timing and steady-state level of atxA expression are critical for optimal toxin and capsule synthesis. Despite the apparent complex control of atxA transcription, only one trans-acting protein, the transition state regulator AbrB, has been demonstrated to interact directly with the atxA promoter. Here we employ 5' and 3' deletion analysis and site-directed mutagenesis of the atxA control region to demonstrate that atxA transcription from the major start site P1 is dependent upon a consensus sequence for the housekeeping sigma factor SigA and an A+T-rich upstream element for RNA polymerase. We also show that an additional trans-acting protein(s) binds specifically to atxA promoter sequences located between -13 and +36 relative to P1 and negatively impacts transcription. Deletion of this region increases promoter activity up to 15-fold. Site-directed mutagenesis of a 9-bp palindromic sequence within the region prevents binding of the trans-acting protein(s), increasing promoter activity 7-fold and resulting in a corresponding increase in AtxA and anthrax toxin production. Notably, an atxA promoter mutant that produced elevated levels of AtxA and toxin proteins during culture was unaffected for virulence in a murine model for anthrax.

3.U03047
Dieser M., Battista J.R., Christner B.C. DNA Double-Strand Break Repair at-15 degrees C // Appl. Environ. Microbiol. 2013. Vol. 79, № 24. P. 7662–7668.

The survival of microorganisms in ancient glacial ice and permafrost has been ascribed to their ability to persist in a dormant, metabolically inert state. An alternative possibility, supported by experimental data, is that microorganisms in frozen matrices are able to sustain a level of metabolic function that is sufficient for cellular repair and maintenance. To examine this experimentally, frozen populations of Psychrobacter arcticus 273-4 were exposed to ionizing radiation (IR) to simulate the damage incurred from natural background IR sources in the permafrost environment from over similar to 225 kiloyears (ky). High-molecular-weight DNA was fragmented by exposure to 450 Gy of IR, which introduced an average of 16 double-strand breaks (DSBs) per chromosome. During incubation at -15 degrees C for 505 days, P. arcticus repaired DNA DSBs in the absence of net growth. Based on the time frame for the assembly of genomic fragments by P. arcticus, the rate of DNA DSB repair was estimated at 7 to 10 DSBs year(-1) under the conditions tested. Our results provide direct evidence for the repair of DNA lesions, extending the range of complex biochemical reactions known to occur in bacteria at frozen temperatures. Provided that sufficient energy and nutrient sources are available, a functional DNA repair mechanism would allow cells to maintain genome integrity and augment microbial survival in icy terrestrial or extraterrestrial environments.

4. U11378
Gao F., Song W., Katz L.A. Genome Structure Drives Patterns of Gene Family Evolution in Ciliates, a Case Study Using Chilodonella Uncinata (protista, Ciliophora, Phyllopharyngea) // Evolution. 2014. Vol. 68, № 8. P. 2287–2295.

In most lineages, diversity among gene family members results from gene duplication followed by sequence divergence. Because of the genome rearrangements during the development of somatic nuclei, gene family evolution in ciliates involves more complex processes. Previous work on the ciliate Chilodonella uncinata revealed that macronuclear -tubulin gene family members are generated by alternative processing, in which germline regions are alternatively used in multiple macronuclear chromosomes. To further study genome evolution in this ciliate, we analyzed its transcriptome and found that (1) alternative processing is extensive among gene families; and (2) such gene families are likely to be C. uncinata specific. We characterized additional macronuclear and micronuclear copies of one candidate alternatively processed gene familya protein kinase domain containing protein (PKc)from two C. uncinata strains. Analysis of the PKc sequences reveals that (1) multiple PKc gene family members in the macronucleus share some identical regions flanked by divergent regions; and (2) the shared identical regions are processed from a single micronuclear chromosome. We discuss analogous processes in lineages across the eukaryotic tree of life to provide further insights on the impact of genome structure on gene family evolution in eukaryotes. by divergent regions; and (2) the shared identical regions are processed from a single micronuclear chromosome. We discuss analogous processes in lineages across the eukaryotic tree of life to provide further insights on the impact of genome structure on gene family evolution in eukaryotes

5.U15400
Gordienko E.N., Kazanov M.D., Gelfand M.S. Evolution of Pan-Genomes of Escherichia coli, Shigella spp., and Salmonella enterica // J. Bacteriol. 2013. Vol. 195, № 12. P. 2786–2792.

Multiple sequencing of genomes belonging to a bacterial species allows one to analyze and compare statistics and dynamics of the gene complements of species, their pan-genomes. Here, we analyzed multiple genomes of Escherichia coli, Shigella spp., and Salmonella enterica. We demonstrate that the distribution of the number of genomes harboring a gene is well approximated by a sum of two power functions, describing frequent genes (present in many strains) and rare genes (present in few strains). The virtual absence of Shigella-specific genes not present in E. coli genomes confirms previous observations that Shigella is not an independent genus. While the pan-genome size is increasing with each new strain, the number of genes present in a fixed fraction of strains stabilizes quickly. For instance, slightly fewer than 4,000 genes are present in at least half of any group of E. coli genomes. Comparison of S. enterica and E. coli pan-genomes revealed the existence of a common periphery, that is, genes present in some but not all strains of both species. Analysis of phylogenetic trees demonstrates that rare genes from the periphery likely evolve under horizontal transfer, whereas frequent periphery genes may have been inherited from the periphery genome of the common ancestor.

6.U15400
Hoffmann T. et al. Osmotic Control of opuA Expression in Bacillus subtilis and Its Modulation in Response to Intracellular Glycine Betaine and Proline Pools // J. Bacteriol. 2013. Vol. 195, № 3. P. 510–522.

Glycine betaine is an effective osmoprotectant for Bacillus subtilis. Its import into osmotically stressed cells led to the buildup of large pools, whose size was sensitively determined by the degree of the osmotic stress imposed. The amassing of glycine betaine caused repression of the formation of an osmostress-adaptive pool of proline, the only osmoprotectant that B. subtilis can synthesize de novo. The ABC transporter OpuA is the main glycine betaine uptake system of B. subtilis. Expression of opuA was upregulated in response to both sudden and sustained increases in the external osmolarity. Nonionic osmolytes exerted a stronger inducing effect on transcription than ionic osmolytes, and this was reflected in the development of corresponding OpuA-mediated glycine betaine pools. Primer extension analysis and site-directed mutagenesis pinpointed the osmotically controlled opuA promoter. Deviations from the consensus sequence of SigA-type promoters serve to keep the transcriptional activity of the opuA promoter low in the absence of osmotic stress. opuA expression was downregulated in a finely tuned manner in response to increases in the intracellular glycine betaine pool, regardless of whether this osmoprotectant was imported or was newly synthesized from choline. Such an effect was also exerted by carnitine, an effective osmoprotectant for B. subtilis that is not a substrate for the OpuA transporter. opuA expression was upregulated in a B. subtilis mutant that was unable to synthesize proline in response to osmotic stress. Collectively, our data suggest that the intracellular solute pool is a key determinant for the osmotic control of opuA expression.

7.U04533
Kwon Y.E. et al. SUMOylation negatively regulates the stability of CHFR tumor suppressor // Biochem. Biophys. Res. Commun. 2013. Vol. 430, № 1. P. 213–217.

CHFR ubiquitin ligase acts as a checkpoint upon DNA damage and its functional inactivation is one of key characteristics of tumor development and metastasis. Despite the crucial role in maintaining genome integrity and cell cycle progression, little is known how CHFR stability is regulated. Here, we showed that CHFR is covalently modified by SUMO-1 at lysine 663 and subsequently destabilized by ubiquitin-proteasome system. While CHFRK663R substitution mutation does not alter its subcellular localization, SUMOylation-defective CHFRK663R-stable cells exhibit substantial growth suppression due to the increased stability of CHFRK663R. Moreover, protein level of CHFR, not CHFRK663R, is rapidly declined under SUMOylation-promoting conditions, and SENP2 deSUMOylating enzyme reverses its SUMO-modification. Collectively, we demonstrated that CHFR stability is regulated by SUMOylation-dependent proteasomal degradation. Therefore, our study underscores the importance of CHFR SUMOylation as a new regulatory mechanism of CHFR and highlights the emerging role of SUMOylation in modulating protein stability.

8.U04533
Lasagna-Reeves C.A. et al. Dual role of p53 amyloid formation in cancer; loss of function and gain of toxicity // Biochem. Biophys. Res. Commun. 2013. Vol. 430, № 3. P. 963–968.

The tumor suppressor p53 plays an important role in genome integrity. It is frequently mutated in all types of human cancers, making p53 a key factor in cancer progression. Two phenotypic consequences of these alterations are dominant; a loss of function and a gain of function of p53, which, in several cases, accumulates in intracellular aggregates. Although the nature of such aggregates is still unclear, recent evidence indicates that p53 can undergo conformational transitions leading to amyloid formation. Amyloid diseases, such as, Alzheimer's disease, are characterized by the accumulation of insoluble aggregates displaying the fibrillar conformation. We decided to investigate the propensity of wild type p53 to aggregate and its consequent assembly into different amyloid species, such as oligomers and fibrils; and to determine if these changes in conformation lead to a loss of function of p53. Furthermore, we analyzed cases of Basal Cell Carcinoma (BCC), for the presence of p53 amyloids. Here, we show that p53 forms amyloid oligomers and fibrils, which coincide with p53 inability of binding to DNA consensus sequences. Both p53 amyloid oligomers and fibrils were detected in BCC cancer samples. Additionally, we demonstrate that p53 oligomers are the most cytotoxic to human cell cultures. Our study reveals p53 amyloid formation and demonstrates its dual roe in the pathogenesis of cancer by producing a loss of protein function and a gain of toxic function, extensively described in several amyloidogenic diseases. Our results suggest that under certain circumstances, cancer could be considered a protein-conformation disease.

9.U12116
Ohadi M., Mohammadparast S., Darvish H. Evolutionary trend of exceptionally long human core promoter short tandem repeats // Gene. 2012. Vol. 507, № 1. P. 61–67.

Short tandem repeats (STRs) are variable elements that play a significant role in genome evolution by creating and maintaining quantitative genetic variation. Because of their proximity to the + 1 transcription start site (TSS) and polymorphic nature, core promoter STRs may be considered a novel source of variation across species. In a genome-scale analysis of the entire human protein-coding genes annotated in the GeneCards database (19,927), we analyze the prevalence and repeat numbers of different classes of core promoter STRs in the interval between 120 and + 1 to the TSS. We also analyze the evolutionary trend of exceptionally long core promoter STRs of >= 6-repeats. 133 genes (similar to 2%) had core promoter STRs of >= 6-repeats. In the majority of those genes, the STR motifs were found to be conserved across evolution. Di-nucleotide repeats had the highest representation in the human core promoter long STRs (72 genes). Tri- (52 genes), tetra-, penta-, and hexa-nucleotide STRs (9 genes) were also present in the descending prevalence. The majority of those genes (84 genes) revealed directional expansion of core promoter STRs from mouse to human. However, in a number of genes, the difference in average allele size across species was sufficiently small that there might be a constraint on the evolution of average allele size. Random drift of STRs from mouse to human was also observed in a minority of genes. Future work on the genes listed in the current study may further our knowledge into the potential importance of core promoter STRs in human evolution.

10.U45336
Paterson R.R.M., Lima N. Biochemical mutagens affect the preservation of fungi and biodiversity estimations // Appl. Microbiol. Biotechnol. 2013. Vol. 97, № 1. P. 77–85.

Many fungi have significant industrial applications or biosafety concerns and maintaining the original characteristics is essential. The preserved fungi have to represent the situation in nature for posterity, biodiversity estimations, and taxonomic research. However, spontaneous fungal mutations and secondary metabolites affecting producing fungi are well known. There is increasing interest in the preservation of microbes in Biological Resource Centers (BRC) to ensure that the organisms remain viable and stable genetically. It would be anathema if they contacted mutagens routinely. However, for the purpose of this discussion, there are three potential sources of biochemical mutagens when obtaining individual fungi from the environment: (a) mixtures of microorganisms are plated routinely onto growth media containing mutagenic antibiotics to control overgrowth by contaminants, (b) the microbial mixtures may contain microorganisms capable of producing mutagenic secondary metabolites, and (c) target fungi for isolation may produce "self" mutagens in pure culture. The probability that these compounds could interact with fungi undermines confidence in the preservation process and the potential effects of these biochemical mutagens are considered for the first time on strains held in BRC in this review.

11.U12116
Qian J. et al. Genome-wide analysis of simple sequence repeats in the model medicinal mushroom Ganoderma lucidum // Gene. 2013. Vol. 512, № 2. P. 331–336.

Simple sequence repeats (SSRs) or microsatellites are one of the most popular sources of genetic markers and play a significant role in gene function and genome organization. We identified SSRs in the genome of Ganoderma lucidum and analyzed their frequency and distribution in different genomic regions. We also compared the SSRs in G. lucidum with six other Agaricomycetes genomes: Coprinopsis cinerea, Laccaria bicolor, Phanerochaete chrysosporium, Postia placenta, Schizophyllum commune and Serpula lacrymans. Based on our search criteria, the total number of SSRs found ranged from 1206 to 6104 and covered from 0.04% to 0.15% of the fungal genomes. The SSR abundance was not correlated with the genome size, and mono- to tri-nucleotide repeats outnumbered other SSR categories in all of the species examined. In G. lucidum, a repertoire of 2674 SSRs was detected, with mono-nucleotides being the most abundant. SSRs were found in all genomic regions and were more abundant in non-coding regions than coding regions. The highest SSR relative abundance was found in introns (108 SSRs/Mb), followed by intergenic regions (84 SSRs/Mb). A total of 684 SSRs were found in the protein-coding sequences (CDSs) of 588 gene models, with 81.4% of them being tri- or hexa-nucleotides. After scanning for InterPro domains, 280 of these genes were successfully annotated, and 215 of them could be assigned to Gene Ontology (GO) terms. SSRs were also identified in 28 bioactive compound synthesis-related gene models, including one 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), three polysaccharide biosynthesis genes and 24 cytochrome P450 monooxygenases (CYPs). Primers were designed for the identified SSR loci, providing the basis for the future development of SSR markers of this medicinal fungus.

12.U12116
Uda K., Ellington W.R., Suzuki T. A diverse array of creatine kinase and arginine kinase isoform genes is present in the starlet sea anemone Nematostella vectensis, a cnidarian model system for studying developmental evolution // Gene. 2012. Vol. 497, № 2. P. 214–227.

Phosphagen (guanidino) kinases (PK) constitute a family of homologous phosphotransferases catalyzing the reversible transfer of the high-energy phosphoryl group of ATP to naturally occurring guanidine compounds. Prior work has shown that PKs can be phylogenetically separated into two distinct groups- an arginine kinase (AK) subfamily and a creatine kinase (CK) subfamily. The latter includes three CK isoforms- cytoplasmic CK (CyCK), mitochondrial CK (MiCK) and three-domain flagellar CK (fCK). In the present study we identified six unique PK genes from the draft genome sequence of the starlet sea anemone Nematostella vectensis, a well-known model organism for understanding metazoan developmental evolution. Using reverse transcription polymerase chain reaction (RTPCR) methods, full length cDNAs were amplified for all of these PKs. These cDNAs were cloned and expressed in Escherichia colt as 6x His-tagged fusion proteins. The six PKs were identified as the three typical CK isoforms (CyCK, MiCK and fCK), two unusual AKs (a two-domain AK (2DAK) and a three-domain AK (3DAK)) and a PK which phosphorylated arginine. The latter enzyme had a very low AK activity (its apparent V-max, value being less than 0.2% that of 3DAK), lacks several key residues necessary for AK enzyme activity, and was tentatively designated as AK1. As far as we know, this constitutes the first report of an AK with the three fused AK domains. The Bayesian tree suggested that the third domain of 3DAK likely evolved from the gene for domain 2 of typical two-domain AK found widely in cnidarians. Construction of phylogenetic trees and comparison of exon-intron organizations of their respective genes indicated that the N. vectensis three-domain fCK and 3DAK evolved independently, and both enzymes are likely to be targeted to cell membranes since they have a myristoylation signal at their respective N-termini. These results complement prior work on other basal invertebrates showing that multiple CK and AK isoform genes were present at the dawn of the radiation of metazoans. The presence of isoform diversity in an organism lacking in structural complexity reflects an early imperative for targeting of PKs to particular cellular contexts such as muscle fibers, neurons, ciliated/flagellated epithelia and spermatozoa.

13.U47153
Webster M.T., Hurst L.D. Direct and indirect consequences of meiotic recombination: implications for genome evolution // Trends in Genetics. 2012. Vol. 28, № 3. P. 101–109.

There is considerable variation within eukaryotic genomes in the local rate of crossing over. Why is this and what effect does it have on genome evolution? On the genome scale, it is known that by shuffling alleles, recombination increases the efficacy of selection. By contrast, the extent to which differences in the recombination rate modulate the efficacy of selection between genomic regions is unclear. Recombination also has direct consequences on the origin and fate of mutations: biased gene conversion and other forms of meiotic drive promote the fixation of mutations in a similar way to selection, and recombination itself may be mutagenic. Consideration of both the direct and indirect effects of recombination is necessary to understand why its rate is so variable and for correct interpretation of patterns of genome evolution.

14.035781
Абдурашитов М.А., Куксова А.Н., Акишев А.Г., Землянская Е.В., Дегтярев С.Х. MTEI-ПЦР-анализ – новый метод определения статуса метилирования GC-богатых регуляторных участков генов-онкосупрессоров человека // Вестник биотехнологии и физико-химической биологии им. Ю.А. Овчинникова. 2013. Т. 9. № 3. С. 15-23.

Предложен новый метод MteI-ПЦР-анализа GC-богатых участков ДНК, основанный на уникальной метилзависимой сайт-специфической ДНК-эндонуклеазе MteI, имеющей протяженный высокометилированный сайт узнавания. Метод включает в себя гидролиз ДНК ферментом MteI с последующим проведением ПЦР либо в реальном времени, либо с определением полученных продуктов методом гель-электрофореза. Установлен статус метилирования регуляторных участков ряда генов-онкосупрессоров методом MteI-ПЦР-анализа в сравнении с ранее предложенным методом BlsI- и GlaI-ПЦР-анализа. Показана применимость метода MteI-ПЦР-анализа для анализа статуса метилирования регуляторных участков генов CEBPD, HS3ST2, RASSF1A, SEPT9b и TWIST1. В случае гена RASSF1A real-time MteI-ПЦР-анализ, в отличие от real-time GlaI- и BlsI-ПЦР-анализа, не обнаруживает метилирования регуляторного участка ДНК в здоровых клетках, что позволяет более четко определять и дискриминировать статус метилирования регуляторного участка как этого гена, так и, вероятно, ряда других GC-богатых участков ДНК человека

15.004425
Глазкова Д.В., Шипулин Г.А. Tale-нуклеазы – новый инструмент для редактирования генома // Молекулярная биология. 2014. Т. 48. № 3. С. 355-370.

Внесение целенаправленных изменений в геном живых клеток или целых организмов позволяет решать множество задач фундаментальной науки, биотехнологии и медицины. “Выключение” генов-мишеней в зиготах дает возможность изучать функции этих генов у различных организмов, а замена отдельных нуклеотидов в ДНК ? исправлять мутации в генах и таким образом лечить наследственные заболевания. Введение гена в нужную область генома можно использовать для получения клеток-продуцентов или организмов с определенными свойствами. Подобные манипуляции с геномами стали возможными после появления технологии, получившей название “редактирование генома”. Эта технология основана на внесении разрыва в определенный участок хромосомной ДНК с помощью эндонуклеазы, распознающей уникальные последовательности, и последующего восстановления целостности ДНК за счет клеточных механизмов репарации. Для редактирования генома необходимы эндонуклеазы с изменяемой специфичностью, способные избирательно расщеплять выбранную последовательность-мишень. Появление нового типа программируемых эндонуклеаз, сконструированных на базе бактериальных белков ? TAL-эффекторов (Transcription Activators Like Effector, TALE), стало важным этапом в развитии технологии редактирования и способствовало широкому распространению ее методов. В настоящем обзоре рассмотрена история открытия TAL-эффекторов и создания TALE-нуклеаз, описаны их преимущества перед полученными ранее эндонуклеазами с цинковыми пальцами. Отдельный большой раздел посвящен описанию генетических модификаций, которые можно осуществлять, используя разные способы редактирования генома.

16.004425
Землянская Е.В., Дегтярев С.Х. Субстратная специфичность и свойства метилзависимых сайт-специфических ДНК-эндонуклеаз // Молекулярная биология. 2013. Т. 47. № 6. С. 900-913.

Метилзависимые сайт-специфические ДНК-эндонуклеазы (МД-эндонуклеазы) ? это немногочисленная группа ферментов, которые специфически расщепляют только метилированную ДНК. Среди них различают N6-метиладенин- и 5-метилцитозинзависимые ферменты. МД-эндонуклеазы изучены мало, но представляют интерес, как для фундаментальных исследований, так и с точки зрения их практического использования в биотехнологии и эпигеномике. В обзоре впервые обобщены данные, касающиеся свойств МД-эндонуклеаз, в особенности субстратной специфичности этих ферментов, а также затрагиваются вопросы участия МД-эндонуклеаз в функционировании бактериальной клетки и возможности практического применения этих ферментов в биотехнологии и эпигеномике.

17.001075
Инге-Вечтомов С.Г. Матричный принцип как парадигма современной генетики // Генетика. 2013. Т. 49. № 1. С. 9-15.

Представления о непрерывности живого, развивавшиеся с середины XIX века, Н.К. Кольцов завершил в 1928 г. концепцией матричного принципа для воспроизведения хромосом. Установление генетической роли нуклеиновых кислот и появление молекулярной генетики увенчались появлением Центральной догмы молекулярной биологии Ф. Крика, которая стала современным воплощением матричного принципа (матрицы I рода). Открытие “белковой наследственности” выдвинуло представление о стерических, или конформационных, матрицах (матрицах II рода) для воспроизведения конформации ряда белков. Таким образом, можно дополнить Центральную догму. В этом модифицированном виде матричный принцип претендует на роль основной парадигмы современной генетики.

18.000513
Смекалова Е.М., Зверева М.Э., Громенко Е.В., Шубернецкая О.C., Рубцова М.П., Донцова О.А. Биосинтез и созревание теломеразной РНК обзор // Биохимия. 2012. Т. 77. № 10. С. 1350-1361.

Теломераза синтезирует повторяющиеся G-богатые последовательности (теломерные повторы) на концах хромосом эукариотических организмов. Этот механизм обеспечивает целостность генома, так как укорочение теломерной ДНК приводит к деградации и слиянию хромосом. Основные компоненты теломеразы - теломеразная каталитическая субъединица и теломеразная РНК, в составе которой присутствует небольшой матричный участок, по которому и осуществляется синтез теломерного повтора на 3'-конце хромосомы. Мутации в теломеразной РНК вызывают дискератоз, а также ассоциированы с некоторыми случаями апластичной анемии, миелодисплазией и диффузным интерстициальным пневмофиброзом. Показано, что теломераза достоверно активна в 85% опухолей, а активация теломеразы является одним из первых шагов на пути трансформации клетки в злокачественную. Изучение работы теломеразы и закономерностей регуляции фермента позволит понять механизм развития многих болезней и разработать новые подходы для их лечения. В данном обзоре мы рассматриваем современное представление о путях биосинтеза, процессинга и функционировании теломеразной РНК в наиболее изученных системах - дрожжах, позвоночных и ресничных простейших организмах.

19.035781
Чернухин В.А., Михненкова Н.А., Ломаковская Е.Н., Шинкаренко Н.М., Дедков В.С., Дегтярев С.Х. Новая сайт-специфическая эндонуклеаза рестрикции BPUN4I узнает и расщепляет последовательность ДНК 5’-G^GNNCC-3’ // Вестник биотехнологии и физико-химической биологии им. Ю.А. Овчинникова. 2013. Т. 9. № 2. С. 5-8.

Из бактериального штамма Bacillus pumilus N4 выделена новая эндонуклеаза рестрикции BpuN4I, определена ее субстратная специфичность и место расщепления ДНК. Эндонуклеаза рестрикции BpuN4I узнает последовательность ДНК 5’-GvGNNCC-3’ и расщепляет ее как указано стрелкой. Фермент, расщепляющий сайт 5’-GGNNCC-3’ с образованием четырех нуклеотидных 5’-липких концов, обнаружен впервые. Рестриктаза BpuN4I является неошизомером фермента NlaIV, имеющего такую же последовательность узнавания, но образующего фрагменты ДНК с тупыми концами

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Шиловский Г.А., Хохлов А.Н., Шрам С.И. Система поли(абр-рибозил)ирования белков: роль в поддержании стабильности генома и детерминации продолжительности жизни обзор // Биохимия. 2013. Т. 78. № 5. С. 573-587.

Известно, что с возрастом усиливаются процессы, приводящие к нарушению целостности генома. Это связано как с увеличенной продукцией активных форм кислорода, так и со снижением эффективности анти-оксидантной защиты и систем поддержания стабильности генома. Накопление с возрастом различных не-репарируемых повреждений генома может являться причиной развития многих возрастных заболеваний и появления фенотипических и физиологических признаков старения. Очевидно также, что существует тесная связь между механизмами поддержания стабильности генома, с одной стороны, и процессами спонтанного опухолеобразования и длительностью жизни, с другой. В этой связи большой интерес вызывает система поли(ADP-рибозил)ирования белков, активируемая в ответ на возникновение различных повреждений ДНК. Накопленные к настоящему времени данные заставляют рассматривать ее в качестве своеобразного координатора клеточных процессов, направляющего клетку по пути выживания или гибели, в зависимости от степени повреждения ДНК. В обзоре обобщены и проанализированы данные, касающиеся участия системы поли(ADP-рибозил)ирования в различных механизмах репарации ДНК, ее взаимодействия с белками прогерий, а также возможной роли в возникновении спонтанных новообразований и детерминации продолжительности жизни. Приведены данные о связи между различными полиморфизмами гена пол^М^-рибоза)-полимеразы-1 человека и долгожительством.

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