title: Homologous recombination between p53 and its pseudogene in a radiation-induced mouse tumor.
abstract: Genome recombination is essential for life; however, its dysfunction causes cancer. Here we report the formation of a chimera structure of the p53 gene due to homologous recombination with the p53 pseudogene in tumors produced by repeated local beta-irradiation of the backs of mice. The recombination occurred near the 5' end of exon 5. Because this tumor carried a 5-bp deletion in exon 6 of the expressed p53 allele, and the defect in p53 is reported to elevate the cellular recombination activity, this chimera formation is thought to be initiated by a radiation-induced DNA double strand break in the p53-mutated cell with enhanced recombination. The abundance of this chimera structure was estimated to be 8% of the total of tumor p53, and the functional p53 side of this chimera had no deletion in exon 6. The indication is that the recombination occurred before the loss of heterozygosity of the mutated p53 allele took place but after a few divisions of the original heterozygous p53-mutated cell toward monoclonal expansion. A novel mechanism of cancer induction is suggested.
authors.affiliation: Genetics Division, National Cancer Center Research Institute, Tokyo, Japan. htanooka@ncc.go.jp
authors.forename: H
authors.initials: H
authors.lastname: Tanooka
authors.forename: A
authors.initials: A
authors.lastname: Ootsuyama
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D001483:Base Sequence; D001610:Beta Particles; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics; D002678:Chimera; D004249:DNA Damage; D005260:Female; D005354:Fibrosarcoma / Q000209:etiology / Q000235:genetics; D016158:Genes, p53; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009381:Neoplasms, Radiation-Induced; D011544:Pseudogenes; D011995:Recombination, Genetic; D017384:Sequence Deletion; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics*