Volker Vogt, Department of Molecular Biology and Genetics

The Vogt laboratory has used avian sarcoma and leukemia viruses (ASLV) as a model system to study how virus particles are made at the site of "budding" at the plasma membrane. Retrovirus particles are composed of products of the viral gaggene (internal structural proteins), polgene (reverse transcriptase and integrase proteins) and envgene (surface glycoproteins). Assembly involves protein-protein, protein-lipid, and protein-RNA-interactions. Only the product of the gag gene is required for formation of particles; env and pol are dispensable (and so is viral RNA). The gag gene product (or "Gag") is translated as a "polyprotein" precursor polypeptide composed of several protein domains.

After assembly and release from the cell, these domains are proteolytically cleaved by the viral protease PR. The domains that will become mature proteins are called MA ("membrane associated"), p10 (function unknown), CA ("capsid"), NC ("nucleocapsid"), and PR. MA interacts somehow with the membrane. CA is believed to form a shell around the ribonucleoprotein complex of genomic RNA and NC protein. NC is a very basic protein with Cys/His motifs that bind RNA. It is the Gag precursor polypeptide that is the major actor in assembly. It must carry information to direct it to the plasma membrane, to interact with other molecules of Gag at the site of budding, to interact specifically with viral RNA, and to interact with the envelope glycoproteins. None of the these interactions is understood except at a crude level.

Nina Winand, College of Veterinary Medicine

Our laboratory is interested in identifying mammalian proteins that participate in recombination during meiosis and in exploring the biochemical events involved in this process. I have recently cloned and characterized the human and murine homologues of the S. cerevisiae MSH5 (mut S homologue 5) gene.

While the MSH5 proteins are structurally related to the bacterial MutS proteins, which initiate DNA mismatch repair by recognizing and binding to mispaired bases, MSH5 is not required for mismatch repair. Yeast msh5 mutants have no apparent defects in mis-match correction, but are instead specifically defective in reciprocal recombination and exhibit high levels of nondisjunction of homologous chromosomes at meiosis I.

Although the function of MSH5 is not yet known, prelim-inary evidence suggests that it is part of a multiprotein complex that interacts with recombination intermediates (such as Holliday junctions) to facilitate their resolution as cross-overs. The pattern of expression of the mammalian MSH5 homologues indicates that they are involved not only in meiotic recombination, but also in mediating antigen receptor gene rearrangements that occur during lymphoid development.