GENETICS OF 5-FLUORODEOXYURIDINE-RESISTANT MUTANTS OF<i>NEUROSPORA CRASSA</i>

Hoffmann, George; Malling, H.V.; Mitchell, Tom

doi:10.1139/g73-097

Cited by 6 publications

(6 citation statements)

References 13 publications

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“…When George Hoffmann was a graduate student in my laboratory, he suggested that we use various antimetabolites to develop forward mutation systems in Neurospora. It turned out to be very feasible [Hoffmann et al, 1973;Malling, 1974, 1975]. After his PhD, George left Oak Ridge and ultimately became a superb educator at Holy Cross College in Massachusetts.…”

Section: Biology Division At Oak Ridge National Laboratory Neurosporamentioning

confidence: 99%

History of the science of mutagenesis from a personal perspective

Malling

2004

Environ and Mol Mutagen

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A career in the study of mutagenesis spanning 50 years is a gift few scientists have been bestowed. My tenure in the field started in 1953, the year the structure of DNA became known (Watson and Crick [1953]: Nature 171:737). Before that time, it was suspected that DNA was the genetic material based on the research of Oswald T. Avery (Avery et al. [1944]: J Exp Med 79:137), but many scientists still believed that proteins or polysaccharides could be the genetic material. The present article describes a lifetime of personal experience in the field of chemical mutagenesis. The methods used to treat viruses with chemical mutagens were well developed in the 1950s. Here I review the early use of nitrous acid and hydroxylamine as mutagens in eukaryotes, the development of methods for the metabolic activation of mutagens by microsomal preparations, and the selection of a mutant tester set for the qualitative characterization of the mutagenic activity of chemicals. These studies provided critical background information that was used by Bruce Ames in the development of his Salmonella/microsome assay, widely known as the Ames test (Ames et al. [1973]: Proc Nat Acad Sci USA 70:2281-2285). This article also describes how a set of diagnostic chemical mutagens was selected and used to identify the molecular nature of gene mutations. Today, DNA sequencing has replaced the use of diagnostic mutagens, but studies of this kind formed the foundation of modern mutation research. They also helped set the stage for the organization of the Environmental Mutagen Society and the Environmental Mutagen Information Center, which are described. The article ends with the development of mammalian single-cell mutation assays, the first system for studying in vivo mutagenesis using recoverable vectors in transgenic animals, other mutation assays in intact mammals, and my thoughts on the critically important area of germ cell mutagenesis. This narrative is not a complete autobiographical account, in that I have selected only those experiences that I feel are important for the history of the field and the edification of today's students. I hope I have shown that science not only is a valuable pursuit but can also be fun, stimulating, and satisfying. A good sense of humor and the knowledge that many discoveries come by serendipity are essential.

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Section: Biology Division At Oak Ridge National Laboratory Neurosporamentioning

confidence: 99%

History of the science of mutagenesis from a personal perspective

Malling

2004

Environ and Mol Mutagen

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“…Involved in regulation of pyr-3, udk, and ud-1. (127) Scored by spotting a conidial suspension on medium containing 4 x 10-5 M filter-sterilized 5-fluorodeoxyuridine (463). f: female fertility Infertile as the female, but fully fertile as the male (fertilizing), parent.…”

Section: Er: Eruptmentioning

confidence: 99%

“…Shows interallelic complementation (127). Scored by spotting conidial suspension on medium containing 4 x 10-5 M 5-fluorodeoxyuridine, filter sterilized (463). Mutant gene CIF-dUrd 7, selected by resistance and called fdu-l (463), is allelic (126).…”

Section: (S04)mentioning

confidence: 99%

Chromosomal loci of Neurospora crassa

Perkins¹,

Radford²,

Newmeyer³

et al. 1982

Microbiol Rev

259

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I I ' ~~~~T h Ñ CiOr(r r N z ADDITIONAL LOCI IN LINKAGE GROUP ILinked to mt (8 to 12%) Linked to mt, acr-3 (5%) Right of arg-i (5/29) Linked to so and aro-8 Right of un-18 Between ad-5 and the centromere Between arg-i (4%) and his-3 (I to 2%) Between In(H4250) and T(39311) Left of mt (23%) Linked to mt (2%) and aza-i (39%o) Left of nit-2 (30%) Left of mt (14%) Linked to un-i (9%), probably to the right Linked to hom (1%), probably to the right Linked to mt (17 to 22%) Between T(NM103) and al-2 (18%) Between T(4540) and cr-2Between thi-i (12 to 20%/6) and ad-9 (5%) Linked to ad-5 (1/54), probably to the left Linked to mt (6%) Linked to cys-5 (<1%), probably to the right Right of ad-9 (12%), linked to al (0/76) Right of his-3 (2%) Between the T(AR173) breakpoints Linked to al-2 (10%) and nic-i (1 to 5%) Linked to ad-9 (0/44); right of thi-i (2%) Linked to mt (5%), probably to the left Linked to al-I (10%) Right of os-i (3%) Between nit,i (5 to 19%) and al-I (6 to 19%io) Linked near arg-i Left of al-2 (25%o) Left of mt (16%) Right of nic-2 (6%) Linked to ad-9 (2%), probably to the right Left of cr-i (15%) Left of mt (10%) Probably between his-2 (3%) and cr-i (3%) Between T(NM103) and the right tip Between mt (20%) and arg-i (1%) Between ad-3 (6%) and al-i (16%) Between his-3 and nic-2 Between cyh-i (5%) and al-I (7%) Linked to cyh-i (18%), al-i (2%), and mb-2 (6%) Between arg-i (3%) and T(39311) Between tre (41%) and ad-9 Linked to mt (9%) Linked to mt (20%) Complex phenotype. Alternative requirements: 2-acetylaminofluorine, certain azo dyes, or certain single amino acids. Cold sensitive. Originated among progeny of a rib-i strain that had become tolerant to 2-acetylaminofluorine.

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“…The medium Wac3 supplemented for the nutritional requirements of the strains crossed. The crosses were incubated for 6 weeks at 25 "C. Preparation of ascospore suspensions was carried out by the procedure of F. J. de Serres (Hoffmann et al 1973). (Jagger,196 I ).…”

Section: E T H O D Smentioning

confidence: 99%

“…Both the sensitive strain and the CI-8AG strains are sensitive to the effects of the pyrimidine analogues, 5-fluorouracil and 5-fluorodeoxyuridine (FdUrd) at concentrations which do not inhibit FdUrd-resistant strains (Hoffmann et al 1973). The amino acid analogue, ~~-4 -m e t h y ltryptophan, at a concentration of I 10 ,ug/ml, is inhibitory to the sensitive strain and to CI-8AG no.…”

Section: R E S U L T Smentioning

confidence: 99%

Mutants of Neurospora crassa Resistant to 8-Azaguanine

Hoffmann

Malling

1974

Journal of General Microbiology

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S U M M A R YUnder conditions of limited-adenine supplementation, 8-azaguanine is a potent inhibitor of purine auxotrophic strains of Neurospora crassa. It is relatively ineffective in prototrophic strains. Spontaneous and u.v.-light-induced mutants, resistant to 8-azaguanine, were obtained in a strain carrying the ad-2, ad-3A7 and ad-3B markers. The resistant mutants grew in the presence of 200 ,ug 8-azaguanine and 2-0 / i g adenine sulphate/ml medium. Inhibition of the sensitive strain is virtually complete under these conditions. Higher adenine sulphate concentrations prevent inhibition of the sensitive strain by 8-azaguanine. Resistance of the new mutants to 8-azaguanine was demonstrated by growth-tube experiments and by plating efficiencies in the presence and in the absence of the inhibitor. Growth-tube experiments were also used to study the reversal of 8-azaguanine induced inhibition by adenine sulphate. The resistance markers in the five strains studied were assigned to linkage group 111. The locus designation aza-3 was given to the resistance marker in a selected mutant of spontaneous origin. Resistance to 8-azaguanine is stable in the presence and in the absence of the inhibitor. In heterokaryons, 8-azaguanine resistance is recessive.

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GENETICS OF 5-FLUORODEOXYURIDINE-RESISTANT MUTANTS OFNEUROSPORA CRASSA

Cited by 6 publications

References 13 publications

History of the science of mutagenesis from a personal perspective

History of the science of mutagenesis from a personal perspective

Chromosomal loci of Neurospora crassa

Mutants of Neurospora crassa Resistant to 8-Azaguanine

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