Aoki H, Sato S, Takanami T, Ishihara T, Katsura I, Takahashi H, Higashitani A
Institute of Genetic Ecology, Tohoku University, Sendai, Japan.
Mol Gen Genet. 2000 Sep;264(1-2):119-26. doi: 10.1007/s004380000291.
An ATM-like gene was identified in the genome of Caenorhabditis elegans. The putative product of the gene, termed Ce-atl-1 (C. elegans ATM-like 1) consists of 2514 amino acid residues. The C-terminal sequence, which contains a PI-3 kinase-like domain, showed good homology with the products of the gene MEC1/ESR1 from budding yeast, the rad3+ gene of fission yeast and mammalian ATM (ataxia-telangiectasia and rad3+ related) genes. The results of RNA-mediated interference indicated that the major phenotype associated with repression of Ce-atl-1 was lethality (approximately 50-80%) during early embryogenesis. Among the surviving progeny, males (XO animals) arose at a high frequency (2-30%). In addition, 5% of oocyte chromosomes demonstrated aneuploidy due to a defect in pre-meiotic chromosomal segregation. Gene expression analyses indicated that Ce-atl-1 mRNA was expressed in all larval stages and that its level increased about fivefold in the adult stage. The adult expression level was decreased in the glp-4 mutant, which is defective in germ line proliferation. Ce-atl-1 was strongly expressed in both the mitotic and meiotic cells of adult gonads. In summary, Ce-atl-1 appears to be important for early embryogenesis, and loss of its function results in a defect in chromosome segregation, similar to what has been observed for AT-related proteins.
在秀丽隐杆线虫的基因组中鉴定出一个类似ATM的基因。该基因的推定产物称为Ce-atl-1（秀丽隐杆线虫ATM样蛋白1），由2514个氨基酸残基组成。其C端序列包含一个PI-3激酶样结构域，与芽殖酵母的MEC1/ESR1基因产物、裂殖酵母的rad3+基因产物以及哺乳动物的ATM（共济失调毛细血管扩张症和rad3+相关）基因产物具有良好的同源性。RNA介导的干扰结果表明，与Ce-atl-1抑制相关的主要表型是早期胚胎发育期间的致死性（约50-80%）。在存活的后代中，雄性（XO动物）出现的频率很高（2-30%）。此外，5%的卵母细胞染色体由于减数分裂前染色体分离缺陷而表现出非整倍性。基因表达分析表明，Ce-atl-1 mRNA在所有幼虫阶段均有表达，且在成虫阶段其水平增加约五倍。在生殖系增殖有缺陷的glp-4突变体中，成虫期的表达水平降低。Ce-atl-1在成年性腺的有丝分裂和减数分裂细胞中均强烈表达。总之，Ce-atl-1似乎对早期胚胎发育很重要，其功能丧失会导致染色体分离缺陷，这与AT相关蛋白的情况类似。
