title: Formation of large deletions by illegitimate recombination in the HPRT gene of primary human fibroblasts.
abstract: HPRT gene mutants were isolated from untreated and x-irradiated cultures of primary human fibroblasts, and mutants carrying large deletions were identified. The breakpoints of the deletions were mapped by methods based on the polymerase chain reaction, and the deletion junctions of four different mutants were sequenced. Alu repeats were associated with one end of three of these junctions, but in each case repeat sequences were not found at the other end. Sequence features found at the deletion breakpoints included in particular short direct and inverted repeats, which may mispair to promote illegitimate recombination. One mutant had additional bases inserted at the deletion junction; these bases formed a direct repeat with a sequence immediately adjacent to the junction, suggesting a mechanism of templated repair of broken DNA in deletion formation.
authors.affiliation: Medical Research Council Radiobiology Unit, Didcot, Oxon, England.
authors.forename: T
authors.initials: T
authors.lastname: Morris
authors.forename: J
authors.initials: J
authors.lastname: Thacker
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005091:Exons; D005347:Fibroblasts / Q000201:enzymology / Q000528:radiation effects; D005809:Genes, Regulator; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D017384:Sequence Deletion; D014965:X-Rays
chemical_list: D009838:Oligodeoxyribonucleotides; D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase