Ben-Ishai R, Scharf R, Sharon R, Kapten I
Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel.
Proc Natl Acad Sci U S A. 1990 Aug;87(16):6039-43. doi: 10.1073/pnas.87.16.6039.
Xeroderma pigmentosum cells, which are deficient in the repair of UV light-induced DNA damage, have been used to clone DNA-damage-inducible transcripts in human cells. The cDNA clone designated pC-5 hybridizes on RNA gel blots to a 1-kilobase transcript, which is moderately abundant in nontreated cells and whose synthesis is enhanced in human cells following UV irradiation or treatment with several other DNA-damaging agents. UV-enhanced transcription of C-5 RNA is transient and occurs at lower fluences and to a greater extent in DNA-repair-deficient than in DNA-repair-proficient cells. Southern blot analysis indicates that the C-5 gene belongs to a multigene family. A cDNA clone containing the complete coding sequence of C-5 was isolated. Sequence analysis revealed that it is homologous to a human cellular sequence encoding the amino-terminal activating sequence of the trk-2h chimeric oncogene [Kozma, S. C., Redmond, S. M. S., Xiao-Chang, F., Saurer, S. M., Groner, B. & Hynes, N. E. (1988) EMBO J. 7, 147-154]. The presence of DNA-damage-responsive sequences at the 5' end of a chimeric oncogene could result in enhanced expression of the oncogene in response to carcinogens.
着色性干皮病细胞缺乏修复紫外线诱导的DNA损伤的能力，已被用于克隆人类细胞中DNA损伤诱导的转录本。命名为pC - 5的cDNA克隆在RNA凝胶印迹上与一个1千碱基的转录本杂交，该转录本在未处理的细胞中含量适中，并且在紫外线照射或用其他几种DNA损伤剂处理后的人类细胞中其合成会增强。C - 5 RNA的紫外线增强转录是短暂的，在较低的通量下发生，并且在DNA修复缺陷细胞中比在DNA修复 proficient细胞中程度更大。Southern印迹分析表明C - 5基因属于一个多基因家族。分离出了一个包含C - 5完整编码序列的cDNA克隆。序列分析显示它与编码trk - 2h嵌合癌基因氨基末端激活序列的人类细胞序列同源[科兹马，S.C.，雷德蒙德，S.M.S.，肖 - 昌，F.，绍勒，S.M.，格罗纳，B. & 海因斯，N.E.（1988年）《欧洲分子生物学组织杂志》7，147 - 154]。嵌合癌基因5'端存在DNA损伤反应序列可能导致癌基因在致癌物作用下表达增强。
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