States J C, Myrand S P
Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
Mutat Res. 1996 Aug 8;363(3):171-7. doi: 10.1016/0921-8777(96)00004-3.
XP12BE is a commonly studied XP-A cell line that exhibits slightly increased resistance to UV compared with the majority of XP-A cell lines. The elevated UV survival is common to a subset of XP-A cell lines and correlates with delayed onset of the neurological disease in patients. We identified the XPA mutations in XP12BE by single strand conformation polymorphism (SSCP) analyses and nucleotide sequencing. XP12BE is a compound heterozygote and both mutations affect mRNA splicing. One mutation is a G to C transversion within the splice donor site of intron 4 that is common to several cell lines from XP-A patients with delayed onset of neurological disease. The other mutation is a G to T transversion at the same position as a G to C transversion in the splice acceptor site of intron 3 that is common in Japanese XP-A patients. We also demonstrated the persistence of the XP12BE mutations in cell line 2-O-A2 which has been shown to express XPA protein. These results suggest that the intron 4 splice donor mutation likely produces some, at least partially functional, XPA protein that accounts for the increased UV survival of XP-A cell lines derived from patients with delayed onset of neurological disease.
XP12BE是一种经常被研究的XP-A细胞系，与大多数XP-A细胞系相比，它对紫外线的抗性略有增加。紫外线存活率升高在一部分XP-A细胞系中很常见，并且与患者神经疾病的延迟发作相关。我们通过单链构象多态性（SSCP）分析和核苷酸测序确定了XP12BE中的XPA突变。XP12BE是一个复合杂合子，两个突变都影响mRNA剪接。一个突变是内含子4剪接供体位点内的G到C颠换，这在一些神经疾病发作延迟的XP-A患者的细胞系中很常见。另一个突变是内含子3剪接受体位点中与G到C颠换相同位置的G到T颠换，这在日本XP-A患者中很常见。我们还证明了XP12BE突变在已被证明表达XPA蛋白的2-O-A2细胞系中持续存在。这些结果表明，内含子4剪接供体突变可能产生了一些至少部分具有功能的XPA蛋白，这解释了神经疾病发作延迟的患者来源的XP-A细胞系紫外线存活率增加的原因。
