Determination of mutation rates in bacteriophage T4 by unneighborly base pairs: Genetic analysis

Conkling, Mark A.; Koch, Robert E.; Drake, John W.

doi:10.1016/0022-2836(80)90192-8

Cited by 12 publications

(6 citation statements)

References 19 publications

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“…All of these processes are potentially sequence dependent in their rate and extent. Indeed, the mutagenic action of (AP) at a given site can be strongly influenced by the identity of the nucleotides in the immediate vicinity (Coulondre et al, 1979) and even by single base pair changes at a considerable distance from the site (Conkling et al, 1980). Insofar as misincorporation of (AP) in vitro is concerned, its strong sequence dependence is documented by our earlier nearest-neighbor work (Pless et al, 1981) and, at a more detailed level, in the present report.…”

Section: Discussionsupporting

confidence: 72%

Influence of local nucleotide sequence on substitution of 2-aminopurine for adenine during deoxyribonucleic acid synthesis in vitro

Pless¹,

Bessman²

1983

Biochemistry

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Three highly purified DNA polymerases, Escherichia coli polymerase I (enzyme A) and the polymerases induced by wild-type T4 phage and by T4 phage mutant L141 (antimutator phenotype), have been examined with respect to their tendency to incorporate the deoxyribonucleotide of 2-aminopurine [(AP)] for deoxyadenylate at specific sites in deoxyribonucleic acid (DNA). Using phi X174 phage DNA as a template and selected phi X174 restriction fragments as specific primers, we synthesized short sequences of phi X174 DNA in vitro by the polymerase of interest, with the 5'-triphosphate of 2-aminopurine deoxyriboside and dATP at equimolar concentration. The relative incorporation of (AP) at the various adenine sites was determined by providing the newly synthesized DNA fragment with a specific terminal radioactive label, subjecting the DNA fragment to thermal depurination as a DNA cleavage reaction highly selective for (AP), and analyzing the resulting radioactive fragments by denaturing gel electrophoresis, autoradiography, and microdensitometry. The L141 polymerase shows very pronounced site-dependent variations in (AP) incorporation. For the wild-type T4 polymerase, the pattern of (AP) incorporation follows the biases seen for the L141 enzyme, although in a less pronounced form. Sequence preferences for (AP) incorporation are least marked for E. coli polymerase I (enzyme A); in several instances, they run counter to the sequence biases observed with the T4 enzymes. For the enzyme showing the most pronounced sequence effects, L141 polymerase, the extent of (AP) incorporation was determined at 57 different sites. No simple principle governing the sequence dependence of (AP) incorporation could be deduced from these results.

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Section: Discussionsupporting

confidence: 72%

Influence of local nucleotide sequence on substitution of 2-aminopurine for adenine during deoxyribonucleic acid synthesis in vitro

Pless¹,

Bessman²

1983

Biochemistry

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“…At least in the cases of T4 (which lacks conventional DNA mismatch repair) and of DNA synthesis in vitro by various polymerases, the rate of formation and/or disposition of a mismatch during synthesis can reasonably be expected to vary as a function of its close neighbors, but the number of template and primer bases contacted by the polymerase and/or proofreading exonuclease is small, so the effects of more distant bases might be expected to extinguish quickly. It was therefore surprising to observe that a particular BPS increased mutation rates at sites separated from it by 11 and 12 intervening bases (Conkling et al 1980;Sugino and Drake 1984 as recently confirmed by unpublished results of G. T. Carver and J. W. Drake).…”

Section: Resultsmentioning

confidence: 68%

Templated Mutagenesis in Bacteriophage T4 Involving Imperfect Direct or Indirect Sequence Repeats

Schultz

Drake

2008

Genetics

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Some mutations arise in association with a potential sequence donor that consists of an imperfect direct or reverse repeat. Many such mutations are complex; that is, they consist of multiple close sequence changes. Current models posit that the primer terminus of a replicating DNA molecule dissociates, reanneals with an ectopic template, extends briefly, and then returns to the cognate template, bringing with it a locally different sequence; alternatively, a hairpin structure may form the mutational intermediate when processed by mismatch repair. This process resembles replication repair, in which primer extension is blocked by a lesion in the template; in this case, the ectopic template is the other daughter strand, and the result is errorfree bypass of the lesion. We previously showed that mutations that impair replication repair can enhance templated mutagenesis. We show here that the intensity of templated mutation can be exquisitely sensitive to its local sequence, that the donor and recipient arms of an imperfect inverse repeat can exchange roles, and that double mutants carrying two alleles, each affecting both templated mutagenesis and replication repair, can have unexpected phenotypes. We also record an instance in which the mutation rates at two particular sites change concordantly with a distant sequence change, but in a manner that appears unrelated to templated mutagenesis. T EMPLATED mutations are initiated when a DNA primer strand dissociates from its cognate template and anneals with a fragment of complementary sequence in an ectopic template. The relocated primer may be extended, acquiring a short sequence that is not fully complementary to the original template, and then reanneal with its cognate template. If the acquired noncomplementary bases escape correctly oriented proofreading and mismatch repair, mutations will result. Lynn Ripley (1982) described two models for templated mutagenesis based on imperfect palindromic repeats, in one of which the ectopic template was in the other parental strand and in the other of which the ectopic template was in the daughter strand itself. Examination of other mutations added imperfect direct repeats as mutagenic templates (Ripley et al. 1986;Shinedling et al. 1987). Templated mutations are usually invoked when they simultaneously acquire multiple changes for which a plausible donor template can be found. Despite the intrinsic fascination of templated complex mutations and their potential importance for certain evolutionary paths and some human genetic disorders, the enzymology that creates them has not been characterized.Template switching also occurs in a mutation-avoiding mode called replication repair. In the canonical model for replication repair (Fujiwara and Tatsumi 1976;Higgins et al. 1976), a primer strand whose extension has been blocked by DNA damage switches to the other daughter strand as a template, extends briefly, and then switches back to its cognate template, thus accurately bypassing the damaged site.In 1987, a mechanism for su...

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“…Because the frequency of multiple events is higher than can be explained by independent events, an alternative explanation is required. One possibility is that a lesion can disrupt DNA structure over an extended range, as in the "unneighborly" base-pairing effect seen by Conkling et al [54]. A second possibility is that there is an SOS-like mechanism for bypassing an adduct that involves a reduction in proofreading and hence multiple distant mutational events.…”

Section: Dmba-induced Mutationmentioning

confidence: 99%

Mutational spectra in the lacl gene in skin from 7, 12‐dimethylbenz[a]anthracene‐treated and untreated transgenic mice

Gorelick

Andrews

et al. 1995

Molecular Carcinogenesis

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Transgenic mice carrying the bacterial lacl gene in a lambda shuttle vector were used to isolate and characterize background and 7,12-dimethylbenz[a]anthracene (DMBA)-induced mutations in skin. Adult male mice were treated once topically with either DMBA or acetone or were left untreated. Seven days later, DMBA treatment had significantly increased the mutant frequency in the skin (mean +/- SEM, 36 +/- 3 x 10(-5)) versus in vehicle-treated (6.4 +/- 1.2 x 10(-5)) and untreated mice (7.1 x 1.0 x 10(-5)). At least 10 mutants from each of three DMBA-treated and three untreated mice were selected for DNA sequence analysis. In each case, the entire 1080-bp target gene was sequenced. Base-pair substitutions predominated (86 of 96 mutations), although frameshift and deletion mutations were also detected. Twelve percent of the mutants carried more than one mutation. In controls, the mutations were predominantly GC-->AT transitions (26 of 42), and no AT-->TA transversions were recovered. In contrast, in the DMBA-treated mice, AT-->TA transversions represented 42% of the mutations (23 of 54) and GC-->AT transitions accounted for only 11%. The AT-->TA transversions occurred mostly at 5'-CA sites. This class of mutation has been recovered frequently in ras genes from DMBA-treated mice and probably represents an early event in carcinogenesis (Nelson MA et al., Proc Natl Acad Sci USA 89:6398-6402, 1992). Our present results are consistent with the types of DNA damage induced by DMBA. The observation of different mutant frequencies and spectra in treated and control mice demonstrates the utility of this approach in the study of mutagenesis in vivo.

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Determination of mutation rates in bacteriophage T4 by unneighborly base pairs: Genetic analysis

Cited by 12 publications

References 19 publications

Influence of local nucleotide sequence on substitution of 2-aminopurine for adenine during deoxyribonucleic acid synthesis in vitro

Influence of local nucleotide sequence on substitution of 2-aminopurine for adenine during deoxyribonucleic acid synthesis in vitro

Templated Mutagenesis in Bacteriophage T4 Involving Imperfect Direct or Indirect Sequence Repeats

Mutational spectra in the lacl gene in skin from 7, 12‐dimethylbenz[a]anthracene‐treated and untreated transgenic mice

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