Fujimori A, Araki R, Fukumura R, Saito T, Mori M, Mita K, Tatsumi K, Abe M
Division of Biology and Oncology, National Institute of Radiological Sciences, Chiba, Japan.
Genomics. 1997 Oct 1;45(1):194-9. doi: 10.1006/geno.1997.4919.
The DNA-PKcs gene encodes the 465-kDa catalytic subunit of DNA-dependent protein kinase (DNA-PK), which associates with heterodimeric autoantigens Ku70 and Ku80 and exhibits protein kinase activity depending on DNA double-strand breaks. The gene is also responsible for the aberration in severe combined immune deficiency (SCID) mice, which exhibit a high sensitivity to ionizing radiation and abnormal DNA rearrangement of immunoglobulin and T cell receptor genes. There is further evidence that DNA-PKcs phosphorylates various proteins involved in DNA replication, transcription, repair, and recombination. Nevertheless the structure/function relationship in this huge molecule is virtually unknown. We determined the exons and introns of the murine DNA-PKcs gene by the long-distance polymerase chain reaction method. The murine DNA-PKcs gene consists of 86 exons distributed in a region of more than 250 kb. The average size of the exons is 140 bp. All the splicing sites conform to the GT/AG rule. The SCID mutation site (Tyr4046) has been identified in exon 85. The genomic structure of the DNA-PKcs gene provides clues for the study of various functional domains in this macromolecule.
DNA-PKcs基因编码DNA依赖性蛋白激酶（DNA-PK）的465-kDa催化亚基，该亚基与异二聚体自身抗原Ku70和Ku80结合，并根据DNA双链断裂表现出蛋白激酶活性。该基因还与严重联合免疫缺陷（SCID）小鼠的异常有关，这些小鼠对电离辐射高度敏感，免疫球蛋白和T细胞受体基因的DNA重排异常。进一步的证据表明，DNA-PKcs可磷酸化参与DNA复制、转录、修复和重组的各种蛋白质。然而，这个巨大分子中的结构/功能关系实际上尚不清楚。我们通过长距离聚合酶链反应方法确定了小鼠DNA-PKcs基因的外显子和内含子。小鼠DNA-PKcs基因由86个外显子组成，分布在超过250 kb的区域。外显子的平均大小为140 bp。所有剪接位点均符合GT/AG规则。已在第85外显子中鉴定出SCID突变位点（Tyr4046）。DNA-PKcs基因的基因组结构为研究该大分子中的各种功能域提供了线索。
