PUBLICATION
DNA damage response and Ku80 function in the vertebrate embryo
- Authors
- Bladen, C.L., Lam, W.K., Dynan, W.S., and Kozlowski, D.J.
- ID
- ZDB-PUB-050602-6
- Date
- 2005
- Source
- Nucleic acids research 33(9): 3002-3010 (Journal)
- Registered Authors
- Kozlowski, David J.
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Antigens, Nuclear/chemistry
- Antigens, Nuclear/genetics
- Antigens, Nuclear/physiology*
- DNA Damage*
- DNA Repair*
- DNA-Binding Proteins/chemistry
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/physiology*
- Embryo, Nonmammalian/metabolism
- Embryo, Nonmammalian/radiation effects*
- Molecular Sequence Data
- Protein Structure, Tertiary
- RNA, Messenger/metabolism
- Radiation Tolerance
- Radiation, Ionizing
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology*
- PubMed
- 15914672 Full text @ Nucleic Acids Res.
Citation
Bladen, C.L., Lam, W.K., Dynan, W.S., and Kozlowski, D.J. (2005) DNA damage response and Ku80 function in the vertebrate embryo. Nucleic acids research. 33(9):3002-3010.
Abstract
Cellular responses to DNA damage reflect the dynamic integration of cell cycle control, cell-cell interactions and tissue-specific patterns of gene regulation that occurs in vivo but is not recapitulated in cell culture models. Here we describe use of the zebrafish embryo as a model system to identify determinants of the in vivo response to ionizing radiation-induced DNA damage. To demonstrate the utility of the model we cloned and characterized the embryonic function of the XRCC5 gene, which encodes Ku80, an essential component of the nonhomologous end joining pathway of DNA repair. After the onset of zygotic transcription, Ku80 mRNA accumulates in a tissue-specific pattern, which includes proliferative zones of the retina and central nervous system. In the absence of genotoxic stress, zebrafish embryos with reduced Ku80 function develop normally. However, low dose irradiation of these embryos during gastrulation leads to marked apoptosis throughout the developing central nervous system. Apoptosis is p53 dependent, indicating that it is a downstream consequence of unrepaired DNA damage. Results suggest that nonhomologous end joining components mediate DNA repair to promote survival of irradiated cells during embryogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping