Elevated DNA double strand breaks and apoptosis in the CNS of scid mutant mice
- 1 March 2001
- journal article
- research article
- Published by Springer Nature in Cell Death & Differentiation
- Vol. 8 (3), 245-255
- https://doi.org/10.1038/sj.cdd.4400806
Abstract
Genetic approaches have provided evidence that DNA end-joining problems serve an essential role in neuronal survival during development of mammalian embryos. In the present study, we tested whether the DNA repair enzyme, DNA dependent protein kinase, plays an important role in the survival of cerebral cortical neurons in mice. DNA-PK is comprised of a DNA-binding subunit called Ku and a catalytic subunit called DNA-PKcs. In mice with the scid mutation, DNA-PKcs is truncated near the kinase domain, which causes loss of kinase activity. We compared the spatial and temporal aspects of neuronal cell death in scid versus isogenic wild-type embryos and found a significant increase in dying cells in scid mice, as assessed by nuclear changes, DNA fragmentation and caspase-3 activity. Additional biochemical and immunocytochemical studies indicated that of several DNA repair enzymes investigated, only PARP was increased in scid mice, possibly in response to elevated DNA strand breaks. Cell Death and Differentiation (2001) 8, 245–255Keywords
This publication has 52 references indexed in Scilit:
- Cell birth, cell death, cell diversity and DNA breaks: how do they all fit together?Trends in Neurosciences, 2000
- Rearranging Views on Neurogenesis: Neuronal Death in the Absence of DNA End-Joining ProteinsNeuron, 1999
- ATM: from gene to functionHuman Molecular Genetics, 1998
- Requirement for an Interaction of XRCC4 with DNA Ligase IV for Wild-type V(D)J Recombination and DNA Double-strand Break Repairin VivoJournal of Biological Chemistry, 1998
- Ku70 Is Required for DNA Repair but Not for T Cell Antigen Receptor Gene Recombination In VivoThe Journal of Experimental Medicine, 1997
- THE GENETIC DEFECT IN ATAXIA-TELANGIECTASIAAnnual Review of Immunology, 1997
- Identification of a nonsense mutation in the carboxyl-terminal region of DNA-dependent protein kinase catalytic subunit in the scid mouse.Proceedings of the National Academy of Sciences, 1996
- Role of poly(ADP-ribose) formation in DNA repairNature, 1992
- The SCID Mouse Mutant: Definition, Characterization, and Potential UsesAnnual Review of Immunology, 1991
- A novel multigene family may encode odorant receptors: A molecular basis for odor recognitionCell, 1991