Suicidal function of DNA methylation in age-related genome disintegration.

摘要: This article is dedicated to the 60th anniversary of 5-methylcytosine discovery in DNA. Cytosine methylation can affect genetic and epigenetic processes, works as a part genome-defense system has mutagenic activity; however, biological functions this enzymatic modification are not well understood. review will put forward hypothesis that host-defense role DNA silencing mutational destroying retroviruses other intragenomic parasites was extended during evolution most host genes have be inactivated differentiated somatic cells, where it acquired new function age-related self-destruction genome. The proposed model considers generator 5mC>T transitions induce 40-70% all spontaneous mutations multiple classes at CpG CpNpG sites flanking nucleotides p53, FIX, hprt, gpt human some transgenes. accumulation 5mC-dependent explains: global changes structure vertebrate genome throughout evolution; loss 5mC from various species over their lifespan Hayflick limit normal cells; polymorphism sites, including asymmetric mCpNpN sites; cyclical demethylation genes. suicidal may special mechanism for increasing damage programmed disintegration responsible cell apoptosis organism aging death.