title: Role of various DNA repair pathways in chromosomal inversion formation in CHO mutants.
abstract: OBJECTIVE
  In an effort to better understand the formation of chromosomal inversions, we investigated the role of various DNA repair pathways, including the non-homologous end joining (NHEJ), homologous recombination (HR), and Fanconi Anemia (FA) repair pathways for the formation of radiation induced chromosomal inversions.
  
  
  METHODS
  CHO10B2 wild type, CHO DNA repair-deficient, and CHO DNA repair-deficient corrected mutant cells were synchronized into G1 phase and exposed to gamma-rays. First post-irradiation metaphase cells were analyzed for chromosomal inversions by a differential chromatid staining technique involving a single cycle pre-irradiation ethynyl-uridine treatment and statistic calculations.
  
  
  RESULTS
  It was observed that inhibition of the NHEJ pathway resulted in an overall decrease in the number of radiation-induced inversions, roughly a 50% decrease when compared to the CHO wild type. Interestingly, inhibition of the FA pathway resulted in an increase in both the number of spontaneous inversions and the number of radiation-induced inversions observed after exposure to 2 Gy of ionizing radiation. It was observed that FA-deficient cells contained roughly 330% (1.24 inversions per cell) more spontaneous inversions and 20% (0.4 inversions per cell) more radiation-induced inversions than the wild-type CHO cell lines. The HR mutants, defective in Rad51 foci, showed similar number of spontaneous and radiation-induced inversion as the wild-type cells. Gene complementation resulted in both spontaneous and radiation-induced inversions resembling the CHO wild-type cells.
  
  
  CONCLUSIONS
  We have concluded that the NHEJ repair pathway contributes to the formation of radiation-induced inversions. Additionally, through an unknown molecular mechanism it appears that the FA signal pathway prevents the formation of both spontaneous and radiation induced inversions.
authors.affiliation: a Department of Environmental and Radiological Health Sciences , Colorado State University , Fort Collins , USA.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Cartwright
authors.affiliation: a Department of Environmental and Radiological Health Sciences , Colorado State University , Fort Collins , USA.
authors.forename: Takamitsu A
authors.initials: TA
authors.lastname: Kato
mesh_terms: D000818:Animals; D016466:CHO Cells; D007446:Chromosome Inversion / Q000528:radiation effects*; D006224:Cricetinae; D003412:Cricetulus; D004260:DNA Repair / Q000528:radiation effects*; D010641:Phenotype
keywords: DNA repair; Fanconi Anemia; Inversion; homologous recombination (HR); non-homologous end joining (NHEJ)