A human cellular sequence implicated in trk oncogene activation is DNA damage inducible.
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.
Ben-Ishai
R
R
Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel.
Scharf
R
R
Sharon
R
R
Kapten
I
I
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D005786:Gene Expression Regulation; D015723:Gene Library; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D015513:Oncogene Proteins / Q000235:genetics*; D009857:Oncogenes / Q000528:radiation effects; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger; D012016:Reference Values; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic / Q000528:radiation effects; D014983:Xeroderma Pigmentosum / Q000235:genetics*
D015513:Oncogene Proteins; D012333:RNA, Messenger; C065400:oncogene protein trk; D011061:Poly A; D012313:RNA; D004247:DNA