DNA damage response and Ku80 function in the vertebrate embryo

Catherine L. Bladen, Wai K. Lam, William S. Dynan, David J Kozlowski

Research output: Contribution to journalArticle

71 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3002-3010
Number of pages9
JournalNucleic Acids Research
Volume33
Issue number9
DOIs
StatePublished - Nov 3 2005

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DNA Damage
Vertebrates
DNA End-Joining Repair
Embryonic Structures
Zebrafish
Central Nervous System
Apoptosis
Gastrulation
Cell Cycle Checkpoints
Ionizing Radiation
Cell Communication
DNA Repair
Genes
Embryonic Development
Retina
Cell Survival
Cell Culture Techniques
Messenger RNA

ASJC Scopus subject areas

  • Genetics

Cite this

DNA damage response and Ku80 function in the vertebrate embryo. / Bladen, Catherine L.; Lam, Wai K.; Dynan, William S.; Kozlowski, David J.

In: Nucleic Acids Research, Vol. 33, No. 9, 03.11.2005, p. 3002-3010.

Research output: Contribution to journalArticle

Bladen, Catherine L. ; Lam, Wai K. ; Dynan, William S. ; Kozlowski, David J. / DNA damage response and Ku80 function in the vertebrate embryo. In: Nucleic Acids Research. 2005 ; Vol. 33, No. 9. pp. 3002-3010.
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