Deletion mapping of highly conserved transcribed sequence downstream from APRT locus

To investigate the nature of DNA sequence rearrangements occurring in a highly malignant human colorectal carcinoma cell line (SW620) exhibiting a high level of chromosome instability, we characterized the molecular basis of deletions eliminating APRT. Deletions in SW620 resembled those in a variety of cell lines. They were joined at regions of little similarity through mono-, di-, or trinucleotide repeats. Breakpoint regions were rich in di- and trinucleotide repeats that might constitute pause sites for the replication complex. Deletions ranged in size from 1.8 to approximately 70 kb and were "directional" in that they eliminated sequences upstream of APRT but not downstream. Analysis of downstream sequences suggested that this pattern of deletion was due to the presence of another gene. Transcripts from these two genes converged but did not overlap. Given that this gene was not deleted in any hamster or human mutants, it appears essential for cell viability. This organization has important consequences for the pattern of mutation and repair of this region.