Analysis of the rearrangements associated with carcinogen-induced activation of the hamster thymidine kinase gene.
We have previously shown that chemical carcinogen treatment of RJK92 hamster cells activates the quiescent thymidine kinase (TK) gene and that 20% of the TK+ variants have a rearrangement in the region 5' to the TK gene (Barr et al. (1986) Mol. Cell. Biol. 6, 3023-3033). After cloning the wild type 5' region to obtain detailed mapping data and hybridization probes, we localized the rearrangement breakpoints by Southern blot analysis to a 1.5 kb region 6 kb 5' to the origin of transcription. This analysis also demonstrated that the rearrangements consist at least partly of a deletion of wild type sequences 5' to this breakpoint region. The region near the transcription origin in the rearranged TK genes has a DNase I-sensitive chromatin conformation and a DNase I hypersensitive site as well as the previously described domain of demethylation (Ibid.). Though this domain of demethylation extends into the breakpoint region, the rearranged region is not associated with DNase I sensitivity nor hypersensitive sites. The rearrangement also does not detectably alter the growth-related regulation of TK activity in these cells.
Barr
F G
FG
Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA 19111.
Rajagopalan
S
S
Lieberman
M W
MW
D000818:Animals; D015139:Blotting, Southern; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D002843:Chromatin / Q000648:ultrastructure; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D006224:Cricetinae; D004249:DNA Damage; D005786:Gene Expression Regulation / Q000187:drug effects; D015321:Gene Rearrangement / Q000187:drug effects*; D008745:Methylation; D015183:Restriction Mapping; D013937:Thymidine Kinase / Q000235:genetics*
D002273:Carcinogens; D002843:Chromatin; D013937:Thymidine Kinase