Extrachromosomal rDNA circle

Extrachromosomal rDNA circles (aka ERC) are extrachromosomal circular DNA (eccDNA), are self replicating sequences of ribosomal DNA (rDNA) found in a strain of yeast, Saccharomyces cerevisiae, and are suggested to contribute to their aging and found in their aged cells. By intra-molecular homologous recombination of the chromosome, eccDNA are formed as well as ERCs. The process for intra-molecular homologous recombination is independent of chromosomal replication. The de novo generated circles had exact multiples of tandem copies of 2-kb fragments from cosmid templates and that the tandem organization was a prerequisite to circle formation. Looping out of organized ribosomal genes in intergenic nontranscribed spacers yielded either large or small repeat circles dependent on large or short repeats of the spacer. Extrachromosomal rDNA circles (aka ERC) are extrachromosomal circular DNA (eccDNA), are self replicating sequences of ribosomal DNA (rDNA) found in a strain of yeast, Saccharomyces cerevisiae, and are suggested to contribute to their aging and found in their aged cells. By intra-molecular homologous recombination of the chromosome, eccDNA are formed as well as ERCs. The process for intra-molecular homologous recombination is independent of chromosomal replication. The de novo generated circles had exact multiples of tandem copies of 2-kb fragments from cosmid templates and that the tandem organization was a prerequisite to circle formation. Looping out of organized ribosomal genes in intergenic nontranscribed spacers yielded either large or small repeat circles dependent on large or short repeats of the spacer. The Sgs1 gene mutations in yeast mother cells were shown to have accelerated aging, suggesting their function to cellular senescence. ERCs accumulate in old cells and mutations of Sgs1 were found to increase this accumulation, leading to the idea that ERCs lead to shorter lifespan of cells. Vice versa, deletion of Fob1 slows down ERC accumulation and increases lifespan. Accumulated ERCs impair cell proliferation in old cells by interfering with the expression of important cell cycle genes at the G1/S transition and thus delay cell cycle progression . The ERC accumulate in the mother cell during the budding process. Sinclair et al. mentioned a suggested common mechanism between the Sgs1 and WRN genes since they both had age related effects on yeast and human aging respectively. Borghouts et al., resolved the two mechanisms, retrograde response and the increase in cellular content of ERCs, that affected longevity in yeast. They determined that the generation of ERCs negatively influence the life spans of grande (cells with fully functional mitochondria) and petite (cells with dsyfunctional mitochondria) yeast strains. Circular extrachromosomal DNA are not only found in yeast but other eukaryotic organisms. A regulated formation of eccDNA in preblastua Xenopus embryos has been developed. The population of circular rDNA is decreased in embryos, indicative of the circular rDNA migrating to linear DNA, as was shown in their analysis on 2D gel electrophoresis. The decrease in circular rDNA and the degradation of the amplified rDNA population in early embryo development indicated that the small circular molecules are homologous to the rDNA gene cluster, meaning that an abundance of rDNA sequences are not prone to generating circular chromosomes from random events like breakage of ligation. Retrograde response or (regulation) is the general term for mitochondrial signaling and broadly defined as the cellular responses to changes in the functional state of the mitochondria. Poole et al. provided a model that resolves the role of retrograde response in lifespan. They depict a process in which ERC production occurs and shortens lifespan in the TAR1 gene.