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Molecular mechanisms of the origin of micronuclei from extrachromosomal elements.

In addition to micronuclei that are formed from chromosomal material (the chromosome-type micronuclei), there are also micronuclei formed from extrachromosomal elements [the double minute (DM)-type micronuclei]. These two types of micronuclei are distinct entities, which exist and arise independently in a cell. A DM is a large extrachromosomal element that consists of amplified genes that are commonly seen in cancer cells; the aggregates of DMs can eventually be expressed as DM-type micronuclei. The question of how the DM-type micronuclei arise was answered by uncovering the quite unique intracellular behaviour of DMs during the cell cycle progression. This behaviour of DMs appeared to be common among the broad spectrum of extrachromosomal elements of endogenous, exogenous or artificial origin. Therefore, studying the biology of DM-type micronuclei will enable us to understand how these extrachromosomal structures may be retained within a cell or expelled from the nucleus and eliminated from the cell. This knowledge could also be used for the treatment of cancers and the development of a new mammalian host-vector system.