Relationship between Type I and Type II Template Processes: Amyloids and Genome Stability
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Relationship between Type I and Type II Template Processes: Amyloids and Genome Stability Yu. V. Andreychuka, *, S. P. Zadorskya, b, A. S. Zhukc, E. I. Stepchenkovaa, b, and S. G. Inge-Vechtomova, b aVavilov
Institute of General Genetics, St. Petersburg branch, Russian Academy of Sciences, St. Petersburg, 199034 Russia bSt. Petersburg State University, St. Petersburg, 199034 Russia c ITMO University, St. Petersburg, 197101 Russia *e-mail: [email protected] Received April 11, 2020; revised May 6, 2020; accepted May 8, 2020
Abstract—Classical views of hereditary mechanisms consider linear nucleic acids, DNA and RNA, as template molecules wherein genetic information is encoded by the sequence of nitrogenous bases. The template principle embodied in the central dogma of molecular biology describes the allowed paths of genetic information transfer from nucleic acids to proteins. The discovery of prions revealed an additional hereditary mechanism whereby the spatial structure is transmitted from one protein molecule to another independently of the sequence of nitrogenous bases in their structural genes. The simultaneous existence of linear (type I) and conformational (type II) templates in one cell inevitably implies their interaction. The review analyzes the current data confirming the idea that protein amyloid transformation may influence the genome stability and considers potential mechanisms of interactions between type I and type II template processes. Special attention is paid to the joint contribution of the two process to tumor “evolution” and the mechanisms of genome destabilization due to amyloid transformation of proteins in Alzheimer’s and Parkinson’s diseases and Down syndrome. Keywords: amyloid, prion, mutation, aneuploidy, genome stability, amyloid neurodegenerative diseases DOI: 10.1134/S0026893320050027
TEMPLATE PRINCIPLE: TYPE I (LINEAR) AND TYPE II (SPATIAL) TEMPLATES The template principle is now the main paradigm of genetics (and total biology). The template principle is embodied in Crick’s central dogma (CD) of molecular biology (Fig. 1a) [1, 2]. Crick considered the transfer of genetic information in the cell (allowable transfer paths are shown with arrows in Fig. 1a, which illustrates the CD). Paying homage to the genius of Crick, it is still better to read the meaning rather than the words alone. Backward information transfer from proteins to RNA and DNA actually takes place in the cell as well. This is regulation. Copying the carriers of information occurs via template processes (TPs) and is, in fact, the process that proceeds exclusively in the directions shown with arrows in the CD scheme. The role that the CD plays in modern biology has been considered in detail elsewhere [3–5]. As a result of thorough investigation, common (universal) characteristics were observed for the three TPs (replication, transcription, and translation) that Abbreviations: Aβ, amyloid β; ALS, amyotrophic lateral sclerosis; AP, apurine site; ROS, reactive oxygen species; AD, Alzheimer’s disease; PD,
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