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Inactivation of bacteriophage lambda and lambda DNA by nitrogen mustard.

M J Fraser, K Ainley, J H Parish

    Mutation Research
    |October 1, 1982
    PubMed
    Summary

    Bacteriophage lambda inactivation by nitrogen mustard is mainly due to DNA-protein cross-linking. This mechanism is crucial for understanding bifunctional alkylating agents

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    Area of Science:

    • Molecular Biology
    • Virology
    • Biochemistry

    Background:

    • Alkylating agents are used in antiviral and cytotoxic therapies.
    • Bacteriophage lambda serves as a model system for studying DNA damage and repair.

    Purpose of the Study:

    • To investigate the inactivation mechanism of bacteriophage lambda and its DNA by alkylating agents, specifically nitrogen mustard (HN2).
    • To elucidate the role of DNA-protein cross-linking in phage inactivation.

    Main Methods:

    • Treatment of bacteriophage lambda and lambda DNA with nitrogen mustard (HN2).
    • Assaying phage survival by infectivity and DNA survival by in vitro assembly of infectious phage particles.
    • Analyzing inactivation kinetics and determining activation energies using Arrhenius plots.

    Main Results:

    • Phage lambda was more sensitive to HN2 than lambda DNA.
    • HN2-induced inactivation of lambda DNA showed biphasic kinetics, with the second phase sensitive to recA, polA, and uvrB mutations.
    • Activation energies indicated that HN2 inactivation of intact phage correlated with DNA-protein cross-linking.

    Conclusions:

    • The primary mechanism for bacteriophage lambda inactivation by nitrogen mustard is DNA-protein cross-linking.
    • These findings have implications for the design and understanding of bifunctional DNA-reactive antiviral and cytotoxic compounds.

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