AID/APOBEC–dependent somatic hypermutation and DNA rearrangements of immunoglobulin and non-immunoglobulin genes
| Autor: | Kolotova T. Yu., Makarenko, V.D., Sorokoumova, L.K., Davidenko M., B. |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
dna editing
lcsh:R5-920 non-coding rna aid/apobec family of deaminases superenhancers transcription factors AID/APOBEC family of deaminases DNA editing Ig genes somatic hypermutation Ig class switching recombination gene AID/APOBEC off-targets double-stranded DNA breaks histone epigenetic modifications non-coding RNA aid/apobec off-targets ig genes somatic hypermutation ig class switching recombination gene double-stranded dna breaks lcsh:Medicine (General) |
| Zdroj: | Anali Mečnikìvsʹkogo Institutu, Iss 4, Pp 6-19 (2019) |
| ISSN: | 1993-4327 |
| Popis: | Editing Ig genes by activation induced deaminase (AID) initiates the antibody diversification process in B lymphocytes. In mammalian B cells, this process includes somatic hypermutation (SHM) and class switch recombination (CSR). The activity of AID is largely confined to switch regions and Ig variable regions but now it is well established that AID/APOBEC-dependent damage and double DNA breaks leading to genome rearrangements and somatic mutagenesis are pervasive throughout the B cell genome. In this review, we focus on the molecular mechanisms that guide AID/APOBEC mutator to physiological and non-physiological targets. Epigenetic modifications, such as histone post-translational modifications and DNA methylation, cis-elements of DNA and the transcription factors that bind to it, which form regulatory clusters and superenhancers, synthesis of non-coding RNA and features of the transcription mode are involved in targeting of AID/APOBEC deaminases to Ig and non-Ig locus. However, not one of the studied factors is specific for the AID target loci. Thus, to date, there is insufficient clarity on the question of what determines the genetically programmed activity of AID in Ig loci and the genetically unprogrammed activity of AID/APOBEC family deaminases in non-Ig loci. The study of AID/APOBEC-dependent somatic hypermutation and rearrangements of Ig and non-Ig locus have both fundamental biological and applied medical significance. The fundamental significance is that the mechanisms of genetic rearrangements in somatic cells can provide a key to understanding the patterns of evolutionary variability of living organisms. The applied value is that based on the data obtained on the genomic instability of non-Ig loci, methods can be developed that suppress the instability of the genome during carcinogenesis and slow down the formation of chemotherapy resistant variants. |
| Databáze: | OpenAIRE |
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