High frequency induction of mitotic recombination by ionizing radiation in Mlh1 null mouse cells

Qi Wang, Olga N. Ponomareva, Michael Lasarev, Mitchell S. Turker

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)189-198
Number of pages10
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume594
Issue number1-2
DOIs
StatePublished - Feb 22 2006

Keywords

  • Autosomal mutation
  • Ionizing radiation
  • Mismatch repair
  • Mitotic recombination

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

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