Hypothetical roles of gene function clusters in the Ty3 lifecycle. Genes identified in this screen for Ty3 mutants are shown. (A) Galactose-induced Ty3-HIS3 transposition depends upon trafficking functions. Ty3 VLPs form perinuclear clusters. Accumulation of VLPs in clusters is postulated to be directly or indirectly dependent upon an intact endosomal trafficking system. Disruption of this localization could interfere with nuclear delivery or uncoating. In this illustration MVBs are shown with associated ESCRT complexes, which mediate intralumenal vesicle budding, but ESCRT complexes could function separately from those specialized vesicles in facilitating Ty3 VLP formation or delivery. N indicates nucleus; ER, endoplasmic reticulum; G, Golgi; SV, secretory vesicle; E, endosome; MVB, multivesicular body; and V, vacuole. See text for details. (B) Ty3 transposition depends upon Rad24 function but is disrupted by proteins associated with the lagging strand clamp-loader, Elg1. Ty3 preintegration complexes entering the nucleus are postulated to distribute between disassembly by replication clamp-mediated activity and integration facilitated by repair. This competition is postulated to be influenced by the relative activity of Elg1 replication clamp-loading and Rad24 checkpoint and repair clamp loading activities.