Ludwig D L, Mudgett J S, Park M S, Perez-Castro A V, MacInnes M A
Life Sciences Division, MS M888, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA.
Mamm Genome. 1996 Sep;7(9):644-9. doi: 10.1007/s003359900198.
The mouse XPG gene is a homolog of the human DNA excision repair gene known to be defective in the hereditary sun-sensitive disorder xeroderma pigmentosum (group-G). Defects in mouse XPG have been shown to directly affect the sensitivity of cultured cells to chemotherapy agents and may play a role in tumor cell drug resistance in vivo. A full-length cosmid clone of mouse XPG was isolated by complementation of the UV sensitivity and repair defect in CHO-UV135 cells. Exon mapping determined that the gene consisted of 15 exons within 32 kb of genomic DNA. Sequencing of intron-exon boundaries revealed that mouse XPG possesses a rare class of intron previously identified in only four other eukaryotic genes; it utilizes AT and AC dinucleotides instead of the expected GT and AG within the splice junctions. Promoter analysis determined that mouse XPG is expressed constitutively and probably initiates transcription from multiple start sites, yet, unlike the yeast homolog RAD2, we found no evidence that it is UVC inducible in cultured cells. Amino acid comparison with human XPG identified a highly conserved acidic region of homology not previously described.
小鼠XPG基因是人类DNA切除修复基因的同源物，已知该基因在遗传性日光敏感疾病色素性干皮病（G组）中存在缺陷。已表明小鼠XPG基因的缺陷会直接影响培养细胞对化疗药物的敏感性，并可能在体内肿瘤细胞的耐药性中起作用。通过补充CHO-UV135细胞中的紫外线敏感性和修复缺陷，分离出了小鼠XPG的全长黏粒克隆。外显子定位确定该基因由基因组DNA 32 kb内的15个外显子组成。内含子-外显子边界的测序表明，小鼠XPG具有一类罕见的内含子，此前仅在其他四个真核基因中鉴定到；它在剪接连接处使用AT和AC二核苷酸，而不是预期的GT和AG。启动子分析确定小鼠XPG基因组成型表达，可能从多个起始位点启动转录，然而，与酵母同源物RAD2不同，我们没有发现它在培养细胞中被UVC诱导的证据。与人类XPG的氨基酸比较确定了一个以前未描述的高度保守的同源酸性区域。
