Laurencon Anne, Orme Charisse M, Peters Heather K, Boulton Christina L, Vladar Eszter K, Langley Sasha A, Bakis Emmanuel P, Harris David T, Harris Nathan J, Wayson Sarah M, Hawley R Scott, Burtis Kenneth C
Section of Molecular and Cellular Biology, University of California, Davis, California 95616, USA.
Genetics. 2004 May;167(1):217-31. doi: 10.1534/genetics.167.1.217.
In a screen for new DNA repair mutants, we tested 6275 Drosophila strains bearing homozygous mutagenized autosomes (obtained from C. Zuker) for hypersensitivity to methyl methanesulfonate (MMS) and nitrogen mustard (HN2). Testing of 2585 second-chromosome lines resulted in the recovery of 18 mutants, 8 of which were alleles of known genes. The remaining 10 second-chromosome mutants were solely sensitive to MMS and define 8 new mutagen-sensitive genes (mus212-mus219). Testing of 3690 third chromosomes led to the identification of 60 third-chromosome mutants, 44 of which were alleles of known genes. The remaining 16 mutants define 14 new mutagen-sensitive genes (mus314-mus327). We have initiated efforts to identify these genes at the molecular level and report here the first two identified. The HN2-sensitive mus322 mutant defines the Drosophila ortholog of the yeast snm1 gene, and the MMS- and HN2-sensitive mus301 mutant defines the Drosophila ortholog of the human HEL308 gene. We have also identified a second-chromosome mutant, mus215(ZIII-2059), that uniformly reduces the frequency of meiotic recombination to <3% of that observed in wild type and thus defines a function required for both DNA repair and meiotic recombination. At least one allele of each new gene identified in this study is available at the Bloomington Stock Center.
在一项新的DNA修复突变体筛选中,我们测试了6275个携带纯合诱变常染色体的果蝇品系(从C. Zuker处获得)对甲磺酸甲酯(MMS)和氮芥(HN2)的超敏反应。对2585个第二染色体品系的测试中,我们获得了18个突变体,其中8个是已知基因的等位基因。其余10个第二染色体突变体仅对MMS敏感,定义了8个新的诱变敏感基因(mus212 - mus219)。对3690个第三染色体的测试中,我们鉴定出60个第三染色体突变体,其中44个是已知基因的等位基因。其余16个突变体定义了14个新的诱变敏感基因(mus314 - mus327)。我们已着手在分子水平上鉴定这些基因,并在此报告已鉴定出的前两个基因。对HN2敏感的mus322突变体定义了酵母snm1基因在果蝇中的直系同源基因,对MMS和HN2敏感的mus301突变体定义了人类HEL308基因在果蝇中的直系同源基因。我们还鉴定出一个第二染色体突变体mus215(ZIII - 2059),它能一致地将减数分裂重组频率降低至野生型观察值的<3%,从而定义了DNA修复和减数分裂重组所需的一种功能。本研究中鉴定出的每个新基因至少有一个等位基因可在布鲁明顿果蝇品系中心获得。