Nucleic Acids Research, 1990, Vol. 18, No. 1 129-135
© 1990
MOLECULAR BIOLOGY |
Analysis of the rearrangements associated with carcinogen-induced activation of the hamster thymidine kinase gene
1Department of Pathology, Fox Chase Cancer Center Philadelphia, PA 19111, USA 2Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania Philadelphia, PA 19104, USA
* To whom correspondence should be addressed at: Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA
Received September 18, 1989. Accepted November 27, 1989.
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 dernethylation (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.
+ Present address: Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA