Lee M P, Brown S D, Chen A, Hsieh T S
Department of Biochemistry, Duke University Medical Center, Durham, NC 27710.
Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6656-60. doi: 10.1073/pnas.90.14.6656.
Both biochemical and genetic experiments suggest that the type I DNA topoisomerase may participate in DNA replication, recombination, transcription, and other aspects of DNA metabolism. Despite its apparent importance, genetic studies in unicellular organisms including eubacteria and yeasts indicate that topoisomerase I is not essential for viability. We have previously isolated the cDNA clone encoding DNA topoisomerase I from Drosophila melanogaster. We report here the cytogenetic mapping of top1 to the X chromosome at 13C1 and isolation of top1 genomic DNA. Using P-element mutagenesis, we have isolated a mutant deficient in Drosophila topoisomerase I functions. Genetic studies of this mutant show that topoisomerase I is essential for the growth and development of the fruit fly, a multicellular organism. The biological functions of topoisomerase I are inferred from our analysis of the regulation of topoisomerase I expression during Drosophila development.
生化和遗传学实验均表明,I型DNA拓扑异构酶可能参与DNA复制、重组、转录以及DNA代谢的其他方面。尽管其重要性显而易见,但在包括真细菌和酵母在内的单细胞生物中的遗传学研究表明,拓扑异构酶I对于生存力并非必不可少。我们之前已从黑腹果蝇中分离出编码DNA拓扑异构酶I的cDNA克隆。我们在此报告top1在X染色体上13C1处的细胞遗传学定位以及top1基因组DNA的分离。利用P因子诱变,我们分离出了一个果蝇拓扑异构酶I功能缺陷的突变体。对该突变体的遗传学研究表明,拓扑异构酶I对于多细胞生物果蝇的生长和发育至关重要。我们通过分析果蝇发育过程中拓扑异构酶I表达的调控来推断其生物学功能。