TK{sup {minus}} mutants attributable to localized gene conversion in a human cell line
- Univ. of California, Riverside, CA (United States)
The human lymphoblastoid cell line TK6 is heterozygous at the tk gene, carrying an inactivating frameshift near the end of the coding sequence, within exon 7 of the functional allele. Here, we describe our use of sequence analyses at these polymorphic sites to identify 8 x-ray induced mutations, out of 184 examined, which exhibit partial conversion of the tk functional allele to the non-functional sequence. These mutants are characterized by loss of heterozygosity at the exon 4 frameshift polymorphism, and remain heterozgousity at exon 7. No restriction fragment length alterations were observed by Southern blotting, and sequencing of the tk cDNA in these mutants revealed the presence of two full length tk transcripts, both having the sequence of the non-functional allele in exon 4, but representing the two different sequences in exon 7. Therefore, the results cannot be explained by a partial deletion of the functional tk allele. Polymorphic microsatellite markers located both proximally and distally to tk on the q arm of chromosome 17 were found to remain heterozygous, ruling out the possibility of a single homologous exchange event. These mutants may be explained by single strand invasion coupled with mismatch repair of the resultant heteroduplex, or by recombinationally mediated repair of a double strand break or gap. We also present microsatellite mapping data which localizes the human tk gene to a 1cM region between markers D17S802 and D17S937.
- OSTI ID:
- 115122
- Report Number(s):
- CONF-9503160-; ISSN 0893-6692; TRN: 95:004640-0014
- Journal Information:
- Environmental and Molecular Mutagenesis, Vol. 25, Issue Suppl.25; Conference: 26. annual Environmental Mutagen Society meeting, St. Louis, MO (United States), 12-16 Mar 1995; Other Information: PBD: 1995
- Country of Publication:
- United States
- Language:
- English
Similar Records
X-rays induce interallelic homologous recombination at the human thymidine kinase gene
Genetic instability on chromosome 16 in a Human B lymphoblastoid cell line