Abstract
NATIONAL INSTITUTES OF HEALTh, BETHESDA, MD 20892, USA. The replication cycle of retro- viruses 1 and their retrotransposon relatives involves the insertion of a DNA copy of their RNA genome into a chromosome of the host cell. Although no specific DNA se- quence is required at the site of in- tegration, the distribution of inser- tions is nonrandom. The degree of target site selectivity varies between retroelements2; while some can apparently integrate at essentially any location in the host DNA, others integrate almost exclusively at a limited set of sites. Recent work has begun to reveal how the sites of insertion are determined. The integration machinery Integration of retroviral DNA occurs by a specialized DNA re- combination reaction mediated by the viral integration machinery 3,4 (Fig. 1). An infecting retrovirus carries into the cell a package of tools needed for the subsequent steps of reverse transcription and integration of the resulting linear viral DNA into the host genome. Before integration, the viral DNA exists as part of a large nucleopro- tein complex, the integration com- plex, derived from the viral core. An important component of this integration complex is the viral integrase (IN) protein. This protein alone can carry out the central DNA cutting and joining steps of the integration reaction in vitro. However, the higher order struc- ture of the integration complex, which may contain other proteins in addition to integrase, is likely to be required for the high efficiency and fidelity of integration in vivo. Retrotransposons, such as the Tyl and Ty3 elements of Saccharo- mvces cerevisiae 5, differ from retro- viruses in that there is no extra- cellular phase in their replication cycle. However, like retroviruses, the DNA made by reverse tran- scription forms part of a large nucleoprotein complex 5.6 and the mechanism of DNA integration appears to differ little between these two classes of element. Integration sites in the target
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