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Paradoxical decrease in mutant frequencies and chromosomal rearrangements in a transgenic lacZ reporter gene in Ku80 null mice deficient in DNA double strand break repair. Mutat Res 2003 Aug 28;529(1-2):51-8

Date

08/29/2003

Pubmed ID

12943919

DOI

10.1016/s0027-5107(03)00108-8

Abstract

Repair of DNA double strand breaks (DSB), either by homologous recombination (HR) or nonhomologous end-joining (NHEJ), is essential to maintain genomic stability. To examine the impact of NHEJ deficiency on genomic integrity in Ku80 null (Ku-) mice, the chromosomally integrated shuttle vector pUR288, which includes a lacZ reporter gene, was used to measure mutations in vivo. Unexpectedly, a significant decrease was found in mutant frequencies of Ku- liver (5.04x10(-5)) and brain (4.55x10(-5)) compared to tissues obtained from normal (Ku+) littermates (7.92x10(-5)and 7.30x10(-5), respectively). No significant difference was found in mutant frequencies in spleen from Ku- (7.21x10(-5)) and Ku+ mice (8.16x10(-5)). The determination of the mutant spectrum in lacZ revealed the almost complete absence of chromosomal rearrangements (R) in Ku- tissues (0.5%, 3/616), a notable distinction from Ku+ controls (16.7%, 104/621). These findings suggest that accurate repair of DSB by HR and elimination of cells with unrepaired DNA damage by apoptosis are capable of maintaining genomic stability of the lacZ reporter in Ku- mice.

Author List

Rockwood LD, Nussenzweig A, Janz S

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antigens, Nuclear
Autoantigens
Brain
Chromosome Mapping
Crosses, Genetic
DNA Helicases
DNA Repair
DNA-Binding Proteins
Gene Rearrangement
Genes, Reporter
Ku Autoantigen
Liver
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Mutation
Plasmids
Spleen
beta-Galactosidase
jenkins-FCD Prod-399 190a069c593fb5498b7fcd942f44b7bc9cdc7ea1