Amyloids are highly ordered protein aggregates that can attach monomeric molecules of the same protein with a change of its native conformation. Amyloid fibrils are enriched with β-layers and are resistant to proteinases and detergents. The main interest in the study of amyloids is associated with their association with a number of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. Amyloids can also perform biologically positive functions in various organisms. The role of amyloids and amyloid-like oligomers in the formation of biofilms in bacteria, melanin synthesis, and long-term memory in animals is shown. In yeast Saccharomyces cerevisiae and other fungi, amyloids are transmitted in cell generations and are carriers of protein heredity.
During previous studies conducted in our laboratory, due to the novel yeast test-system [1], amyloid properties for mammalian proteins Rad51 and PHC3 (isoforms 5 and 6) has been shown.
Protein PHC3 is one of the key components of the polycomb group (PcG) - a complex necessary to maintain the repressive state of many genes, including Hox genes during the development of the body. We believe that amyloid aggregation of short isoforms of the PHC3 protein can lead to amyloidization of its full-sized isoform and regulate genes expression level.
The Rad51 protein is one of the main proteins of the DNA double-strand break repair system. We believe that Rad51 aggregation may affect genome stability in normal and cancer cells.
This work is aimed at studying the amyloid properties of human Rad51 protein and short isoforms of the PHC3 protein in vitro, in human cell cultures, human tissues, as well as studying the functional effects of amyloidization of these proteins.
The reported study was funded by RFBR, projects № 19-34-90153 and № 18-04-00799. Also this research was supported by Saint-Petersburg State University grant 15.61.2218.2013