A TY1 INTEGRASE NUCLEAR-LOCALIZATION SIGNAL REQUIRED FOR RETROTRANSPOSITION

Ty1 retrotransposition in Saccharomyces cerevisiae requires integrase (IN)-mediated insertion of Ty1 cDNA into the host genome. The transpos ition components are assembled in the cytoplasm and must cross the nuc lear envelope to reach the genomic target, since, unlike animal cell n uclear membranes, the yeast cell nuclear membrane remains intact throu ghout the cell cycle. We have identified a bipartite nuclear localizat ion signal (NLS) in IN required for Ty1 transposition (Ty1 IN) that di rects IN to the nucleus. Mutations in the NLS that specifically abolis h nuclear localization inactivate transpositional integration but do n ot affect reverse transcription, protein processing, or catalytic acti vity in vitro, No additional Ty1-encoded proteins are required for IN nuclear localization, Intragenic complementation experiments suggest t hat Ty1 IN functions as a multimer and contains two distinct domains, one required for integration and the other for nuclear localization. N uclear targeting of the preintegration complex by an IN NLS may prove to be a general strategy used by retrotransposons and retroviruses tha t infect nondividing cells.