title: An N-terminal deletion mutant of simian virus 40 (SV40) large T antigen oligomerizes incorrectly on SV40 DNA but retains the ability to bind to DNA polymerase alpha and replicate SV40 DNA in vitro.
abstract: A peptide encompassing the N-terminal 82 amino acids of simian virus 40 (SV40) large T antigen was previously shown to bind to the large subunit of DNA polymerase alpha-primase (I. Dornreiter, A. Höss, A. K. Arthur, and E. Fanning, EMBO J. 9:3329-3336, 1990). We report here that a mutant T antigen, T83-708, lacking residues 2 to 82 retained the ability to bind to DNA polymerase alpha-primase, implying that it carries a second binding site for DNA polymerase alpha-primase. The mutant protein also retained ATPase, helicase, and SV40 origin DNA-binding activity. However, its SV40 DNA replication activity in vitro was reduced compared with that of wild-type protein. The reduction in replication activity was accompanied by a lower DNA-binding affinity to SV40 origin sequences and aberrant oligomerization on viral origin DNA. Thus, the first 82 residues of SV40 T antigen are not strictly required for its interaction with DNA polymerase alpha-primase or for DNA replication function but may play a role in correct hexamer assembly and efficient DNA binding at the origin.
authors.affiliation: Institute for Biochemistry, Munich, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Weisshart
authors.forename: M K
authors.initials: MK
authors.lastname: Bradley
authors.forename: B M
authors.initials: BM
authors.lastname: Weiner
authors.forename: C
authors.initials: C
authors.lastname: Schneider
authors.forename: I
authors.initials: I
authors.lastname: Moarefi
authors.forename: E
authors.initials: E
authors.lastname: Fanning
authors.forename: A K
authors.initials: AK
authors.lastname: Arthur
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism; D004257:DNA Polymerase II / Q000378:metabolism*; D004261:DNA Replication; D004279:DNA, Viral / Q000378:metabolism*; D009154:Mutation; D013539:Simian virus 40 / Q000276:immunology* / Q000502:physiology; D014779:Virus Replication
chemical_list: D000952:Antigens, Polyomavirus Transforming; D004279:DNA, Viral; D004257:DNA Polymerase II; D000251:Adenosine Triphosphatases; D004265:DNA Helicases