Abstract
The relation between DNA replication and the action of the mutagen N-methyl-N'-nitro-N-nitroso-guanidine has been studied in Saccharomyces cerevisiae. The frequenceis of reversion to prototrophy of six auxotrophic markers located along one arm of chromosome VII were examined as a function of the vegetative cell cycle. Exponentially growing cells were treated with nitrosoguanidine and then separated by zonal rotor centrifugation into fractions equivalent to stages in the cell cycle. The frequency of reversion for five of the six markers is greatest during the period of DNA replication. Each marker has a single point of maximum reversion, approximately 10-fold greater than the frequency observed at other points in the cell cycle. For any one marker the effect of nitrosoguanidine is restricted to an interval shorter than the period of DNA replication. The two markers most distant from each other, ade5 and leul, both have their highest reversion frequency early during DNA replication. The peak reversion frequency for lys5 is somewhat later, while the peaks for tyr3 and trp5 occur near the end of DNA replication. The results indicate that nitrosoguanidine acts primarily during DNA replication and that different markers appear to be affected at different intervals during the DNA biosynthetic period. If nitrosoguanidine does act at the growing point of DNA replication, these observations indicate that the initiation of DNA replication occurs at specific times during the period of DNA synthesis and at specific initiation sites. Further, there must be more than one point of initiation of DNA replication on one arm of chromosome VII.
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Selected References
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- BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bicknell J. N., Douglas H. C. Nucleic acid homologies among species of Saccharomyces. J Bacteriol. 1970 Feb;101(2):505–512. doi: 10.1128/jb.101.2.505-512.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brusick D. J. Induction of cycloheximide-resistant mutants in Saccharomyces cerevisiae with N-methyl-N'-nitro-N-nitrosoguanidine and ICR-170. J Bacteriol. 1972 Mar;109(3):1134–1138. doi: 10.1128/jb.109.3.1134-1138.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Callan H. G. DNA replication in the chromosomes of eukaryotes. Cold Spring Harb Symp Quant Biol. 1974;38:195–203. doi: 10.1101/sqb.1974.038.01.023. [DOI] [PubMed] [Google Scholar]
- Cerdá-Olmedo E., Hanawalt P. C., Guerola N. Mutagenesis of the replication point by nitrosoguanidine: map and pattern of replication of the Escherichia coli chromosome. J Mol Biol. 1968 May 14;33(3):705–719. doi: 10.1016/0022-2836(68)90315-x. [DOI] [PubMed] [Google Scholar]
- Dawes I. W., Carter B. L. Nitrosoguanidine mutagenesis during nuclear and mitochondrial gene replication. Nature. 1974 Aug 30;250(5469):709–712. doi: 10.1038/250709a0. [DOI] [PubMed] [Google Scholar]
- Fogel S., Mortimer R. K. Recombination in yeast. Annu Rev Genet. 1971;5:219–236. doi: 10.1146/annurev.ge.05.120171.001251. [DOI] [PubMed] [Google Scholar]
- Halvorson H. O., Carter B. L., Tauro P. Synthesis of enzymes during the cell cycle. Adv Microb Physiol. 1971;6(0):47–106. [PubMed] [Google Scholar]
- Hartwell L. H., Culotti J., Reid B. Genetic control of the cell-division cycle in yeast. I. Detection of mutants. Proc Natl Acad Sci U S A. 1970 Jun;66(2):352–359. doi: 10.1073/pnas.66.2.352. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hohlfeld R., Vielmetter W. Bidirectional growth of the E. coli chromosome. Nat New Biol. 1973 Apr 4;242(118):130–132. doi: 10.1038/newbio242130a0. [DOI] [PubMed] [Google Scholar]
- Huberman J. A., Riggs A. D. On the mechanism of DNA replication in mammalian chromosomes. J Mol Biol. 1968 Mar 14;32(2):327–341. doi: 10.1016/0022-2836(68)90013-2. [DOI] [PubMed] [Google Scholar]
- Kriegstein H. J., Hogness D. S. Mechanism of DNA replication in Drosophila chromosomes: structure of replication forks and evidence for bidirectionality. Proc Natl Acad Sci U S A. 1974 Jan;71(1):135–139. doi: 10.1073/pnas.71.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Newlon C. S., Petes T. D., Hereford L. M., Fangman W. L. Replication of yeast chromosomal DNA. Nature. 1974 Jan 4;247(5435):32–35. doi: 10.1038/247032a0. [DOI] [PubMed] [Google Scholar]
- OGUR M., ROSEN G. The nucleic acids of plant tissues; the extraction and estimation of desoxypentose nucleic acid and pentose nucleic acid. Arch Biochem. 1950 Feb;25(2):262–276. [PubMed] [Google Scholar]
- Schwartz M., Worcel A. Reinitiation of chromosome replication in a thermosensitive DNA mutant of Escherichia coli. II. Synchronization of chromosome replication after temperature shifts. J Mol Biol. 1971 Oct 28;61(2):329–342. doi: 10.1016/0022-2836(71)90383-4. [DOI] [PubMed] [Google Scholar]
- Sebastian J., Carter B. L., Halvorson H. O. Use of yeast populations fractionated by zonal centrifugation to study the cell cycle. J Bacteriol. 1971 Dec;108(3):1045–1050. doi: 10.1128/jb.108.3.1045-1050.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]