Defective embryonic neurogenesis in Ku-deficient but not DNA-dependent protein kinase catalytic subunit-deficient mice
Copyright policy )Defective embryonic neurogenesis in Ku-deficient but not DNA-dependent protein kinase catalytic subunit-deficient mice
Mammalian nonhomologous DNA end joining employs Ku70, Ku80, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), XRCC4, and DNA ligase IV (Lig4). Herein, we show that Ku70 and Ku80 deficiency but not DNA-PKcs deficiency results in dramatically increased death of developing embryonic neurons in mice. The Ku-deficient phenotype is qualitatively similar to, but less severe than, that associated with XRCC4 and Lig4 deficiency. The lack of a neuronal death phenotype in DNA-PKcs-deficient embryos and the milder phenotype of Ku-deficient versus XRCC4- or Lig4-deficient embryos correlate with relative leakiness of residual end joining in these mutant backgrounds as assayed by a V(D)J recombination end joining assay. We conclude that normal development of the nervous system depends on the four evolutionarily conserved nonhomologous DNA end joining factors.
- University of California, San Francisco United States
- Harvard University United States
- University of California, San Diego United States
- Harvard Medical School United States
- Howard Hughes Medical Institute United States
Central Nervous System, Cerebral Cortex, Neurons, DNA Ligases, DNA Helicases, Nuclear Proteins, Antigens, Nuclear, Apoptosis, DNA-Activated Protein Kinase, Fibroblasts, Mice, Mutant Strains, DNA-Binding Proteins, DNA Ligase ATP, Mice, Phenotype, In Situ Nick-End Labeling, Animals, Diencephalon, Ku Autoantigen, Cells, Cultured
Central Nervous System, Cerebral Cortex, Neurons, DNA Ligases, DNA Helicases, Nuclear Proteins, Antigens, Nuclear, Apoptosis, DNA-Activated Protein Kinase, Fibroblasts, Mice, Mutant Strains, DNA-Binding Proteins, DNA Ligase ATP, Mice, Phenotype, In Situ Nick-End Labeling, Animals, Diencephalon, Ku Autoantigen, Cells, Cultured
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).166 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!