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Publication : Cloning of the TIS gene suppressed by topoisomerase inhibitors.

First Author  Onishi Y Year  1998
Journal  Gene Volume  215
Issue  2 Pages  453-9
PubMed ID  9714845 Mgi Jnum  J:49547
Mgi Id  MGI:1277684 Doi  10.1016/s0378-1119(98)00313-8
Citation  Onishi Y, et al. (1998) Cloning of the TIS gene suppressed by topoisomerase inhibitors. Gene 215(2):453-9
abstractText  We recently cloned the cDNA TIS (topoisomerase inhibitor-suppressed) in RVC lymphoma cells exposed to the topoisomerase inhibitors. To elucidate the suppression mechanism of the TIS mRNA by camptothecin, we characterized the structures of the TIS gene. The gene spanned about 21 kb including 11 exons and was present as a single copy. The putative transcription site was present 192 bp upstream from the ATG codon. The typical TATA sequence and CCAAT promoter element were located at positions -21 and -81, respectively. The unidirectional deletion analysis of the 5'-flanking region revealed that [-132/+160] is the promoter region, which participates in the responsiveness to camptothecin. A Northern blot analysis showed that the TIS was expressed in most mouse tissues; at the highest level in the liver and to less extent in the heart and skeletal muscle. The present study showed that the expression of the TIS is suppressed at the transcriptional level by camptothecin. Considering that topoisomerase I is an essential enzyme in mammalian cells, the TIS protein may have an important role in camptothecin toxicity.
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