High frequency induction of mitotic recombination by ionizing radiation in Mlh1 null mouse cells.
Mitotic recombination in somatic cells involves crossover events between homologous autosomal chromosomes. This process can convert a cell with a heterozygous deficiency to one with a homozygous deficiency if a mutant allele is present on one of the two homologous autosomes. Thus mitotic recombination often represents the second mutational step in tumor suppressor gene inactivation. In this study we examined the frequency and spectrum of ionizing radiation (IR)-induced autosomal mutations affecting Aprt expression in a mouse kidney cell line null for the Mlh1 mismatch repair (MMR) gene. The mutant frequency results demonstrated high frequency induction of mutations by IR exposure and the spectral analysis revealed that most of this response was due to the induction of mitotic recombinational events. High frequency induction of mitotic recombination was not observed in a DNA repair-proficient cell line or in a cell line with an MMR-independent mutator phenotype. These results demonstrate that IR exposure can initiate a process leading to mitotic recombinational events and that MMR function suppresses these events from occurring.
Wang
Qi
Q
Center for Research on Occupational and Environmental Toxicology, L606, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
Ponomareva
Olga N
ON
Lasarev
Michael
M
Turker
Mitchell S
MS
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D003434:Crossing Over, Genetic / Q000528:radiation effects*; D004252:DNA Mutational Analysis; D005720:Gamma Rays; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008938:Mitosis / Q000235:genetics* / Q000528:radiation effects*; D000070957:MutL Protein Homolog 1; D009154:Mutation / Q000528:radiation effects; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics* / Q000528:radiation effects
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501485:Mlh1 protein, mouse; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1