Mutator versus antimutator activity of a T4 DNA polymerase mutant distinguishes two different frameshifting mechanisms.

Abstract:

Classical "antimutator" DNA polymerases of bacteriophage T4 were examined for their effects upon frameshift mutation rates at a number of positions within rII cistrons. Their antimutagenic activities reduced frameshift frequencies at a number of sites, but at other sites the opposite occurred: the mutant polymerases exhibited clear mutator activities. This dichotomy reveals the operation of two distinct mechanisms of frameshift mutagenesis that are correlated with the DNA sequences at the frameshift sites. Frameshift mutants subject to the antimutator effects of the mutant polymerase lie in A: T-run DNA sequences, where mutations presumably arise by means of the interstrand DNA misalignments postulated by classical theory. The frameshift mutants produced by the mutator activity of these same polymerases lie in quasipalindromic DNA sequences, where mutations are postulated to arise by aberrant metabolism of DNA secondary structures such as hairpins.

Polymerases:

Topics:

Mutational Analysis, Fidelity

One line summary:

Antimutator type T4 mutants were shown to have frameshift mutator activities among certain quasi-palindromic sequences, while reducing frameshift mutations in the A:T-run DNA sequences.

Status:

new topics/pols set partial results complete validated

Results:

Polymerase Reference Property Result Context
T4 A737V Ripley LS1983 Frameshift Error Rate 4.2 Mutation frequency (relative to WT) Technique: T4 rIIB N-terminal frameshift assay ((rFC41; 1b-b2, a - frameshift))
T4 A737V Ripley LS1983 Frameshift Error Rate 1.5 Mutation frequency (relative to WT) Technique: T4 rIIB N-terminal frameshift assay ((rFC40; 1b-b4, a - frameshift))
T4 A737V Ripley LS1983 Frameshift Error Rate 11 Mutation frequency (relative to WT) Technique: T4 rIIB N-terminal frameshift assay ((rFC47; 1b-b7, a - frameshift))
T4 A737V Ripley LS1983 Frameshift Error Rate 0.13 Mutation frequency (relative to WT) Technique: T4 rII 131 reversion
T4 A737V Ripley LS1983 Frameshift Error Rate 0.48 Mutation frequency (relative to WT) Technique: T4 rII UV6 reversion
T4 A737V Ripley LS1983 Frameshift Error Rate 0.65 Mutation frequency (relative to WT) Technique: T4 rII 114 reversion
T4 A737V Ripley LS1983 Frameshift Error Rate 6 Mutation frequency (relative to WT) Technique: T4 rIIB N-terminal frameshift assay ((rFC11; b1-mb, a + frameshift))
T4 A737V Ripley LS1983 Frameshift Error Rate 3.5 Mutation frequency (relative to WT) Technique: T4 rIIB N-terminal frameshift assay ((rFC7; b3-mb, a + frameshift))
T4 A737V Ripley LS1983 Frameshift Error Rate 22 Mutation frequency (relative to WT) Technique: T4 rIIB N-terminal frameshift assay ((rX146; b6-mb, a + frameshift))
T4 A777V Ripley LS1983 Frameshift Error Rate 0.63 Mutation frequency (relative to WT) Technique: T4 rIIB N-terminal frameshift assay ((rFC41; 1b-b2, a - frameshift)
T4 A777V Ripley LS1983 Frameshift Error Rate 3.4 Mutation frequency (relative to WT) Technique: T4 rIIB N-terminal frameshift assay ((rFC47; 1b-b7, a - frameshift))
T4 A777V Ripley LS1983 Frameshift Error Rate 0.2 Mutation frequency (relative to WT) Technique: T4 rII 131 reversion
T4 A777V Ripley LS1983 Frameshift Error Rate 0.18 Mutation frequency (relative to WT) Technique: T4 rII UV6 reversion
T4 A777V Ripley LS1983 Frameshift Error Rate 0.51 Mutation frequency (relative to WT) Technique: T4 rII 114 reversion
T4 A777V Ripley LS1983 Frameshift Error Rate 1.4 Mutation frequency (relative to WT) Technique: T4 rIIB N-terminal frameshift assay ((rFC11; b1-mb, a + frameshift))
T4 A777V Ripley LS1983 Frameshift Error Rate 2.3 Mutation frequency (relative to WT) Technique: T4 rIIB N-terminal frameshift assay ((rFC7; b3-mb, a + frameshift))
T4 A777V Ripley LS1983 Frameshift Error Rate 125 Mutation frequency (relative to WT) Technique: T4 rIIB N-terminal frameshift assay ((rX146; b6-mc, a + frameshift))

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