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1

Role of epigenetic DNA alterations in the pathogenesis of systemic lupus erythematosus

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Januchowski R., Prokop P., Jagodzinski P. P.
Journal of Applied Genetics
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2004
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vol. 45
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issue 2
237-248
EN
Epigenetic alternations in genomic DNA encompass cytosine methylation in cytosine and guanine (CpG) dinucleotide islands, which are usually extended in the promoter and first exon of genes. The DNA methylation is carried out by DNA methyltransferases (DNMT) and it serves as an epigenetic method of gene expression modulation. The epigenetic alternations in genomic DNA have been implicated in the development of malignant and autoimmune diseases. The epigenetic aberration in regulatory DNA sequences may also be responsible for the emergence of changes in the immune system in patients with systemic lupus erythematosus (SLE). The agents 5-azacytidine (azacitidine) and 5-aza-2?-deoxycytidine (decitabine) belong to inhibitors of methyltransferase. These compounds affect the methylation level of promoter sequences and cause phenotypic changes in peripheral blood mononuclear cells (PBMC), which are similar to those observed in PBMC of SLE patients. The lack of methylcytosine in CpG dinucleotides may be responsible for the antigenic properties of microbial DNA. The presence of low-apoptotic methylated DNA fragments has been identified in plasma of SLE patients. These DNA fragments exhibit antigenic properties and may elicit the humoral response responsible for the flare of SLE. The low methylation of CpG residues in the regulatory sequences may also contribute to the elevated expression of human endogenous retroviruses (HERVs) in PBMC of SLE patients. The HERV components exhibit a profound similarity with nuclear antigens and may be responsible for the enhancement of the production of anti-antinuclear antibodies (ANA). Recent advances in the investigation of epigenetic DNA changes have formed the basis of improved understanding of etiopathogenesis of SLE, which may thereby facilitate improvement in therapeutic principles of this disease.
2

50 years of studies of restriction ? modification systems

100%
Waleron K., Nakonieczna J., Waleron M., Podhajska A. J.
Biotechnologia
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2006
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issue 2
65-88
EN
The basic function of restriction endonucleases and methyltransferases is protection of the host genome against foreign DNA. Their recombination and transposition related functions are still being discussed. Some authors postulate that R-M genes may act as selfish genetic elements. Restriction endonucleases are indispensable tools in molecular biology. As these enzymes recognize DNA sequence very specifically, they serve as a model for protein-DNA interaction. Restriction-modification genes have also played the same role as a model for evolutionary studies as well as protein structure - function relations. So far, there have been more than 3500 bacterial strains studied which possessed R-M genes of more than 280 different specificities towards recognition sequence and cleavage sites. They became a very good commercial product for many biotechnological companies. At present, in a genome sequencing era, R-M genes seem to be much more common than it was thought before.
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