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Nucleotide sequence changes in polyoma virus A gene mutants.

T Thomas, P Vollmer, W R Folk

    Journal of Virology
    |March 1, 1981
    PubMed
    Summary
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    Researchers identified specific genetic mutations in polyoma virus mutants ts-a and ts-25E. These changes cause heat-sensitive large T-antigens, with revertants restoring original DNA sequences.

    Area of Science:

    • Virology
    • Molecular Biology
    • Genetics

    Background:

    • Polyoma viruses are DNA tumor viruses.
    • Large T-antigens are crucial for viral replication and transformation.
    • Thermolabile mutants provide insights into protein function and stability.

    Purpose of the Study:

    • To identify the precise mutational alterations responsible for the thermolabile phenotype in polyoma virus mutants ts-a and ts-25E.
    • To understand the molecular basis of large T-antigen thermosensitivity.

    Main Methods:

    • DNA sequencing to pinpoint nucleotide changes in ts-a and ts-25E mutants.
    • Analysis of amino acid substitutions resulting from identified mutations.
    • Isolation and characterization of revertant viruses to confirm mutation causality.

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    Main Results:

    • In ts-a, a G-to-A transition at nucleotide 2193 resulted in an Alanine to Threonine substitution.
    • In ts-25E, a G-to-T transversion at nucleotide 2883 led to a Glycine to Cysteine substitution.
    • Isolated revertants demonstrated restoration of original nucleotides at these specific positions.

    Conclusions:

    • The identified point mutations are directly responsible for the thermolabile nature of the large T-antigens in ts-a and ts-25E polyoma virus mutants.
    • These findings elucidate specific structure-function relationships within the polyoma virus large T-antigen.