title: p12 tethers the murine leukemia virus pre-integration complex to mitotic chromosomes.
abstract: The p12 protein of the murine leukemia virus (MLV) is a constituent of the pre-integration complex (PIC) but its function in this complex remains unknown. We developed an imaging system to monitor MLV PIC trafficking in live cells. This allowed the visualization of PIC docking to mitotic chromosomes and its release upon exit from mitosis. Docking occurred concomitantly with nuclear envelope breakdown and was impaired for PICs of viruses with lethal p12 mutations. Insertion of a heterologous chromatin binding module into p12 of one of these mutants restored PICs attachment to the chromosomes and partially rescued virus replication. Capsid dissociated from wild type PICs in mitotic cells but remained associated with PICs harboring tethering-negative p12 mutants. Altogether, these results explain, in part, MLV restriction to dividing cells and reveal a role for p12 as a factor that tethers MLV PIC to mitotic chromosomes.
authors.affiliation: Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Elis
authors.forename: Marcelo
authors.initials: M
authors.lastname: Ehrlich
authors.forename: Adi
authors.initials: A
authors.lastname: Prizan-Ravid
authors.forename: Nihay
authors.initials: N
authors.lastname: Laham-Karam
authors.forename: Eran
authors.initials: E
authors.lastname: Bacharach
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002213:Capsid; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D002875:Chromosomes / Q000821:virology*; D015683:Gene Products, gag / Q000235:genetics* / Q000378:metabolism*; D009052:Leukemia Virus, Murine / Q000235:genetics*; D051379:Mice; D008938:Mitosis; D009154:Mutation; D009685:Nuclear Envelope / Q000473:pathology / Q000821:virology; D011485:Protein Binding; D053585:Virus Attachment; D016662:Virus Integration; D014779:Virus Replication / Q000235:genetics
chemical_list: D036022:Capsid Proteins; D002843:Chromatin; C468293:Gag protein p12, moloney murine leukemia virus; D015683:Gene Products, gag