title: Molecular structure of mutations at an autosomal locus in human cells: evidence for interallelic homologous recombination.
abstract: A high proportion of spontaneous mutations at the heterozygous thymidine kinase (TK) locus in a human B-lymphoblast cell line involved loss of the entire active allele. Loss of heterozygosity often extended to other loci on chromosome 17q. The authors have developed a system for analysing the role of homologous recombination and gene conversion in such events. A heteroallelic (TK-/-) cell line containing single + 1 frameshifts in exons 4 and 7 was generated by repeated exposures to ICR-191. Revertant mutations to TK+/- were selected and analysed for the presence or absence or each frameshift as well as changes in linked polymorphic markers on 17q. The molecular changes associated with reversion to TK+ can thus be analysed. Preliminary results indicate that homologous recombination can be detected with this system, though it occurs at low frequency (less than 10(-7]. The authors believe this represents the first quantitative assay for measuring recombination between alleles of a specific intact gene in human cells. It should prove useful in evaluating the potency of various classes of mutagens in inducing recombinational and gene conversion events.
authors.affiliation: Laboratory of Radiobiology, Harvard School of Public Health, Boston, MA 02115.
authors.forename: J B
authors.initials: JB
authors.lastname: Little
authors.forename: M B
authors.initials: MB
authors.lastname: Benjamin
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013937:Thymidine Kinase / Q000235:genetics*
chemical_list: D013937:Thymidine Kinase