Chen X, Yang L, Udar N, Liang T, Uhrhammer N, Xu S, Bay J O, Wang Z, Dandakar S, Chiplunkar S, Klisak I, Telatar M, Yang H, Concannon P, Gatti R A
Department of Pathology, UCLA, School of Medicine 90095-1732, USA.
Mamm Genome. 1997 Feb;8(2):129-33.
Using a magnetic beads-mediated cDNA selection procedure and a fetal brain expression library, we identified a transcriptional unit within a cosmid positive for the marker D11S384. Pursuit of its full-length cDNA led to the cloning of the third candidate gene (CAND3) we studied in our quest for the ataxia-telangiectasia (A-T) gene, ATM. CAND3 spans approximately 140 kb of genomic DNA and is located immediately centrimeric to ATM, with 544 bp of DNA separating the two genes. CAND3 encodes two ubiquitously expressed transcripts of approximately 5.8 kb and approximately 4.6 kb that are divergently transcribed from a promoter region common to ATM. Nucleotide sequence was determined for one of its alternately spliced transcripts. The predicted protein has 1175 amino acids and is novel in sequence, with only weak homologies to transcriptional factors, nucleoporin protein, and protein kinases, including members of the phosphatidylinositol 3-kinase (PI-3 kinase) family. Although neither homology to ATM nor any mutation of CAND3 in A-T patients has been found, the head-to-head arrangement of CAND3 and ATM, with expression of both housekeeping genes from a common stretch of 544 bp intergenic DNA, suggests a bi-directional promoter possibly for co-regulation of biologically related functions. YACs, BACs, cosmids, and STSs are defined to aid in further study of this gene.
利用磁珠介导的cDNA筛选程序和胎儿脑表达文库，我们在对标记D11S384呈阳性的黏粒中鉴定出一个转录单位。对其全长cDNA的追踪导致了我们在寻找共济失调毛细血管扩张症（A-T）基因ATM的过程中研究的第三个候选基因（CAND3）的克隆。CAND3跨越约140 kb的基因组DNA，紧邻ATM着丝粒定位，两个基因之间相隔544 bp的DNA。CAND3编码两种普遍表达且大小分别约为5.8 kb和4.6 kb的转录本，它们从ATM共有的启动子区域反向转录。测定了其一种可变剪接转录本的核苷酸序列。预测的蛋白质有1175个氨基酸，序列新颖，仅与转录因子、核孔蛋白和蛋白激酶（包括磷脂酰肌醇3激酶（PI-3激酶）家族成员）有弱同源性。尽管在A-T患者中未发现CAND3与ATM有同源性，也未发现CAND3有任何突变，但CAND3和ATM的头对头排列，以及两个管家基因从一段544 bp的基因间DNA共同表达，提示可能存在一个双向启动子用于共同调节生物学相关功能。定义了酵母人工染色体（YAC）、细菌人工染色体（BAC）、黏粒和序列标签位点（STS）以辅助对该基因的进一步研究。
