Dean F B, Lian L, O'Donnell M
The Rockefeller University, The Howard Hughes Medical Institute, 1230 York Avenue, New York, New York, 10021, USA.
Genomics. 1998 Dec 15;54(3):424-36. doi: 10.1006/geno.1998.5587.
Mutations in DNA repair/cell cycle checkpoint genes can lead to the development of cancer. The cloning of human homologs of yeast DNA repair/cell cycle checkpoint genes should yield candidates for human tumor suppressor genes as well as identifying potential targets for cancer therapy. The Schizosaccharomyces pombe genes rad17, rad1, and hus1 have been identified as playing roles in DNA repair and cell cycle checkpoint control pathways. We have cloned the cDNA for the human homolog of S. pombe rad17, RAD17, which localizes to chromosomal location 5q13 by fluorescence in situ hybridization and radiation hybrid mapping; the cDNA for the human homolog of S. pombe rad1, RAD1, which maps to 5p14-p13.2; and the cDNA for the human homolog of S. pombe hus1, HUS1, which maps to 7p13-p12. The human gene loci have previously been identified as regions containing tumor suppressor genes. In addition, we report the cloning of the cDNAs for genes related to S. pombe rad17, rad9, rad1, and hus1 from mouse, Caenorhabditis elegans, and Drosophila melanogaster. These include Rad17 and Rad9 from D. melanogaster, hpr-17 and hpr-1 from C. elegans, and RAD1 and HUS1 from mouse. The identification of homologs of the S. pombe rad checkpoint genes from mammals, arthropods, and nematodes indicates that this cell cycle checkpoint pathway is conserved throughout eukaryotes.
DNA修复/细胞周期检查点基因的突变可导致癌症的发生。克隆酵母DNA修复/细胞周期检查点基因的人类同源物,不仅应能产生人类肿瘤抑制基因的候选基因,还能确定癌症治疗的潜在靶点。粟酒裂殖酵母基因rad17、rad1和hus1已被确定在DNA修复和细胞周期检查点控制途径中发挥作用。我们已克隆了粟酒裂殖酵母rad17的人类同源物RAD17的cDNA,通过荧光原位杂交和辐射杂种图谱分析,其定位于染色体位置5q13;克隆了粟酒裂殖酵母rad1的人类同源物RAD1的cDNA,其定位于5p14 - p13.2;克隆了粟酒裂殖酵母hus1的人类同源物HUS1的cDNA,其定位于7p13 - p12。这些人类基因位点先前已被确定为含有肿瘤抑制基因的区域。此外,我们还报告了从小鼠、秀丽隐杆线虫和黑腹果蝇中克隆与粟酒裂殖酵母rad17、rad9、rad1和hus1相关基因的cDNA。这些包括黑腹果蝇的Rad17和Rad9、秀丽隐杆线虫的hpr - 17和hpr - 1,以及小鼠的RAD1和HUS1。从哺乳动物、节肢动物和线虫中鉴定出粟酒裂殖酵母rad检查点基因的同源物,表明这种细胞周期检查点途径在整个真核生物中是保守的。