EXTRACHROMOSOMAL DNA IN MAMMALIAN-CELLS

Extrachromosomal DNA (eDNA) is mammalian cells is represented not only as mitochondrial DNA but also as circular DNA existing both in the nucleus and in the cytoplasm. According to its size eDNA could be divided into two major classes: small polydisperse circular DNAs and large circular DNAs. Small polydisperse circular DNAs sized from 150 to 20 000 base pair are found both in the nucleus and in the cytoplasm. Large circular DNAs from 150 000 to 900 000 base pair are found in the nucleus only. Small polydisperse circular DNAs contain mainly repetitive sequences but occasionally they may contain very low repetitive sequences or uniques. Such sequences may result from intrachromosomal recombinations, replicon misfiring, reverse transcription or fragmentation of chromosomal DNA by endogenous nucleases. Large circular DNAs are known to consist mainly of amplified sequences of oncogenese or MDR genes, which result from the deletion of appropriate regions of chromosomes. The number of copies of eDNA is greater in the malignant cells and in cells at certain stages of differentiation. The increase in copy number of eDNA reflects the intensity of processes in the cells. Autonomous replication of small and large circular DNAs is evident in tumor cells, although not all eDNAs can replicate autonomously. The presence in tumor cells of self-replicating molecules of eDNA, which are distributed in daughter cells independently of chromosomal DNA, determines presumably the high rate of adaptability of these cells to environmental conditions (methastasis and resistance to chemotherapeutic agents). It is quite possible that the existence of amplified copies of oncogenes and some other genes in the form of eDNA can determine some phenotypic characteristics of the transformed cells.