Structure, expression, and mutation of the hypoxanthine phosphoribosyltransferase gene.
Structure, expression, and mutation of the hypoxanthine phosphoribosyltransferase gene.
复制标题
次黄嘌呤磷酸核糖转移酶基因的结构、表达和突变。
DOI：
10.1073/pnas.81.7.2147
复制
发表时间：
1984
影响因子：
11.1
通讯作者：
Caskey,CT
中科院分区：
文献类型：
--
作者：
Melton,DW;Konecki,DS;Brennand,J;Caskey,CT
从基因组文库中分离到野生型小鼠次黄嘌呤磷酸核糖基转移酶（HPRT； IMP：焦磷酸盐磷酸核糖基转移酶，EC 2.4.2.8）基因，并确定其结构。这个X染色体连锁基因长度超过33千碱基，分为9个外显子。所有的外显子序列已经被确定，并且在小鼠神经母细胞瘤细胞系中发现了过量产生突变HPRT蛋白的HPRT cDNA编码序列中的单碱基替换。通过核酸酶S1保护和引物延伸研究，以及通过将基因的5‘端连接到野生型人HPRT cDNA上，产生能够在培养细胞中表达的HPRT迷你基因的功能测定，已经确定了该基因的5’端。通常与真核启动子相关的序列不存在于HPRT基因的直接5'侧区，而是高度富含G+C。这一观察结果讨论了DNA甲基化和x染色体失活之间的可能联系。
The wild-type mouse hypoxanthine phosphoribosyltransferase (HPRT; IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) gene has been isolated from genomic libraries and its structure has been determined. This X chromosome-linked gene is greater than 33 kilobases long and is split into nine exons. All the exon sequences have been determined, and a single-base substitution in the HPRT cDNA coding sequence from a mouse neuroblastoma cell line that overproduces a mutant HPRT protein has been identified. The 5' end of the gene has been defined, both by nuclease S1 protection and primer extension studies and by a functional assay in which an HPRT minigene, capable of expression in cultured cells, was created by ligating the 5' end of the gene onto wild-type human HPRT cDNA. Sequences normally associated with eukaryotic promoters are not present in the immediate 5'-flanking region of the HPRT gene, which is instead highly G+C rich. This observation is discussed in relation to the possible link between DNA methylation and X-chromosome inactivation.