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J W Drake

Publications and source records attributed to J W Drake.

At least 55 records · Page 3Linked to original sources
PubMed1984

Isolation and characterization of conditional alleles of bacteriophage T4 genes uvsX and uvsY.

The bacteriophage T4 uvsW, uvsX and uvsY gene functions are required for wild-type levels of recombination and for normal survival and mutagenesis after treatments with ultraviolet (UV) and ionizing radiations. The ability of uvsX and uvsY mutations to suppress the lethality of gene 49 mutations was used to select temperature-sensitive and amber alleles of these two genes. (uvsW mutations do not suppress gene 49 mutations.) A simple and powerful complementation test was developed to assist in assigning uvs mutations to genes. The amber alleles of uvsX and uvsY behave as simple null alleles, fully suppressing a gene 49 defect, enhancing UV killing and abolishing UV mutagenesis. However, the properties of the ts alleles of uvsX and uvsY demonstrated that suppression of a gene 49 defect, sensitivity to UV-induced inactivation and UV mutability can be partially uncoupled. These results prompt the hypothesis that radiation mutagenesis occurs during DNA chain elongation past template damage within a recombinational intermediate rather than within a conventional replication fork.

Alleles↗
PubMed1984

Thermal rescue of UV-irradiated bacteriophage T4 and biphasic mode of action of the WXY system.

When ultraviolet-irradiated bacteriophage T4 is assayed at plating temperatures ranging from 20 degrees to 40 degrees, its survival increases at the higher temperatures. This "thermal rescue" requires an intact WXY system but not the denV pyrimidine dimer excision system. Mutation rates decrease with increasing temperature, indicating that some lesions processed in a mutagenic manner at lower temperatures are accurately repaired or circumvented at high temperatures. When both the cold sensitivity of UV survival in the wild type and the temperature sensitivity of newly isolated ts mutants of uvsX and uvsY were used, expression of the WXY system was monitored in temperature shift UV survival experiments and was found to be biphasic: the uvsX and uvsY functions increase UV survival in two increments, one at an early and another at a late stage of infection. The uvsW function, however, increases UV survival only early in infection.

DNA Repair↗
PubMed1982

Perspectives in molecular mutagenesis.

The models and paradigms that underlie a vigorously developing science may tend to stifle progress or may serve to sharpen the knife edge of paradox. Working out mutagenic mechanisms is a conceptually and technologically demanding task, and we are accumulating an increasingly uncomfortable number of experimental and theoretical inconsistencies. First, there continue to be widespread difficulties in specifying the chemical nature of mutagenic DNA alterations, both because of the multitude of DNA reaction products induced by many mutagens and because of the intrinsic rarity of most mutational responses. For instance, alkylation of the 0(6) position of guanine to generate adducts of modest dimensions is widely believed to form the basis for the mutagenic and carcinogenic actions of numerous chemicals. However, while this scheme is supported by in vitro evidence, it has failed to explain why bacteriophages can be thus alkylated in vitro by N-methyl-N'-nitro-N-nitrosoguanidine without the production of mutations, or why microbial eukaryotes alkylated by ethyl methanesulfonate or N-methyl-N'-nitro-N-nitrosoguanidine display no mutagenic response when their "error-prone repair systems" are mutationally inactivated. Second, a base pair is typically mutated at vastly different rates, and with different directional specificities, when it resides at different positions within a gene; whereas very little of this variability is explained by current theories that aim to describe the determinants of fidelity in DNA replication. (Some sizable portion of this variation now appears to depend not only upon neighboring base-pair influences but also upon much more subtle and distant effects). Third, experimental modifications of enzymatic fidelity by means of amino acid substitutions, and perhaps also cation replacements, lead to such a diversity of modified mutation rates as to seriously challenge the ability of any simple theory to organize the experimental observations into a coherent and predictive network.

Alkylation↗
PubMed1982

Methyl methanesulfonate mutagenesis in bacteriophage T4.

MMS induces diverse rII mutations from a wild-type background in bacteriophage T4. About 56% are base pair substitutions, about 30% are frameshift mutations, and the remainder is a miscellaneous set of rapidly reverting or leaky mutants of unknown composition; but deletions were not detected. MMS-induced forward mutation is sharply reduced by the mutations px and y, which also reduce ultraviolet, photodynamic and gamma-ray mutagenesis and increase killing by all of these agents. Thus, many of the mutations arise via the T4 WXY system. The induction of G:C leads to A:T transitions was detected even in a px or y background using sensitive reversion tests, and the few forward rII mutations that were induced from this background also behaved like transition mutations. Thus, some MMS-induced mutations arise independently of the WXY system, perhaps as a result of the (rather weak) ability of MMS to alkylate the O6 position of guanine.

Genes, Lethal↗
PubMed1977

Mutator mutations in bacteriophage T4 gene 42 (dHMC hydroxymethylase).

Temperature-sensitive mutations of bacteriophage T4 gene 42 produce diverse effects upon spontaneous mutation rate. G:C vector A:T transition rates are increased, often strongly; frameshift mutation rates are weakly increased; A:T vector G:C transition rates (and perhaps also A:T vector Py:Pu transversion rates) are decreased; and one G:C vector Py:Pu transversion rate is also decreased. These results, together with certain interactions between gene-42 mutator effects and both base analogue mutagenesis and the viral error-prone repair system, suggest that the dHMC hydroxymethylase coded by gene 42 affects mutation rates in a more complex manner than by the simple regulation of the concentration of the DNA precursor dHMCTP.

Base Sequence↗
PubMed1976

Heat mutagenesis in bacteriophage T4: the transversion pathway.

Heat induces transversions (as well as transitions) at G-C base pairs in bacteriophage T4. The target base for transversions is guanine,which is converted to a product which is sometimes replicated and transcribed as a pyrimidine.A model for this process is proposed in which the deoxyguanosine glycosidic bond migrates from N9 to N2: the resulting deoxyneoguanosine may pair with normal guanine to produce G-C leads to C-G transversions.

Base Sequence↗
PubMed1976

Heat mutagenesis in bacteriophage T4: the transition pathway.

G-C leads to A-T transitions are induced by heat, and arise from the deamination of cytosine (5-hydroxymethylcytosine in the case of bacteriophage T4) generating uracil. The reaction is proton-catalyzed, and is also characteristic of acid mutagenesis. Mutation rates and activation energies of mutation are site-specific, and are presumably influenced by neighboring bases. Rates of heat-induced mutation in bacteriophage T4 under conditions of temperature, pH, and ionic strength similar to those prevailing in higher eukaryotic cells suggest that heat mutagenesis may present a serious challenge to organisms with large genomes, and may comprise an important determinant of the rates of spontaneous mutation.

Chemical Phenomena↗
PubMed1976

Gamma-ray mutagenesis in bacteriophage T4.

137Cs-gamma irradiation of bacteriophage T4 induces large deletions plus a variety of types of point mutations. All mutations arise with single-hit kinetics, and all by a misrepair process. The estimated point mutation rate is 1.5 X 10(-9) per locus per rad.

Chromosome Aberrations↗
PubMed1976

The biochemistry of mutagenesis.

Mutagenesis has remained an intriguing aspect of genetics since the beginning of this century, and its analysis has proceeded hand in hand with the elucidation of gene replication and expression. Interest in this area has further heightened with the growing awareness that numerous environmental agents may cause mutations in humans. These mutations may lead to metabolic as well as neoplastic diseases. Advances during the past 15 years have revealed two major classes of mutagenic mechanisms: directly induced base mispairing, and misrepair. Alkylating agents for instance, generate many different reaction products in DNA, but only two of these (O6-alkylguanine and O4-alkylthymine) are likely candidates for directly induced mispairing. He has also turned out to be an important mutagen, one that presents a particular serious challenge to large genomes; it converts cytosine to uracil and guanine to an analogue of cytosine. DNA lesions that interrupt DNA chain elongation, including many of other products of alkylation, often trigger an error-prone postreplication repair process. Current evidence suggests that this process involves in incorrect insertion of bases into gaps in progeny-strand DNA opposite such a lesion. Mutagenic mechanisms are subject to powerful genetic controls that include the activities of DNA polymerases in the selection of deoxynucleoside triphosphates and the removal of incorrectly inserted nucleotides.

Alkylating Agents↗
PubMed1975

Environmental mutagenesis: evolving strategies in the USA.

A recent Environmental Mutagen Society report (the "Committee 17" report) made recommendations regarding the screening of environmental mutagens and the use of the resulting data. It is important in this respect to employ highly sensitive tests which detect heritable genetic damage of all possible molecular types. Mutagens of artificial origin which are being considered for continued production must be characterized with respect to their level and pattern of distribution and their persistence in the environment in order to perform realistic risk evaluations. Risk evaluation itself, particularly the summation of the effects of numerous distinct mutagens, may be assisted by adopting a common measure of mutagenicity such as the REC (rem-equivalent-chemical). Finally, the Committee 17 report laid out highly specific recommendations concerning maximum permissible exposures to environmental mutagens. Federal regulatory agencies and their enabling legislation are in fact evolving toward the effective control of this highly complicated problem.

Environmental Exposure↗
PubMed1974

Misrepair mutagenesis in bacteriophage T4.

The T4 mutations px, y and 1206 inactivate an error-prone recombination-like repair system, reducing or abolishing mutagenesis by UV irradiation, MMS, and white light irradiation in the presence of the photosensitizer 8MOP. Both px and y increase some spontaneous mutation rates and slightly enhance proflavin mutagenesis; neither mutation affects thymineless or 2AP mutagenesis appreciably, but both mildly enhance 5BU mutagenesis. The mutation hm promotes UV, MMS, photodynamic, thymineless, and base analog mutagenesis, in addition to spontaneous base pair substitution mutation. It does not, however, markedly affect proflavin mutagenesis. The px mutation maps in the vicinity of genes 41-56, and the hm mutation maps in the vicinity of genes rI-v.

Adenine↗
PubMed1973

Thymineless mutagenesis in bacteriophage T4.

Thymine deprivation can be achieved in bacteriophage T4 either by the use of the thymidylate synthetase inhibitor FUdR, or by an appropriate combination of genetic blocks; both methods produce marked mutagenesis. Extensive tests of the specificity of thymineless mutagenesis reveal that only A:T base pairs are affected, and that transitions and possibly transversions are produced. This system therefore constitutes the first example of an A:T-specific mutagen. Thymineless mutagenesis in bacteriophage T4 exhibits a marked dependence upon the functional state of the DNA polymerase gene, but is largely independent of the px-y misrepair system.

Adenine Nucleotides↗