The 8-oxoguanine DNA glycosylase 1 (ogg1) decreases the vulnerability of the developing brain to DNA damage
- Authors
- Gu, A., Ji, G., Yan, L., and Zhou, Y.
- ID
- ZDB-PUB-131029-13
- Date
- 2013
- Source
- DNA repair 12(12): 1094-104 (Journal)
- Registered Authors
- Zhou, Yong
- Keywords
- none
- MeSH Terms
-
- Animals
- Brain/abnormalities
- Brain/embryology*
- Brain/physiology
- Cloning, Molecular
- DNA Damage*
- DNA Glycosylases/metabolism*
- DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism*
- Embryo, Nonmammalian
- Gene Expression Regulation, Developmental
- Gene Knockdown Techniques
- Larva/metabolism
- Multifunctional Enzymes/metabolism*
- Oligonucleotide Array Sequence Analysis
- Oxidative Stress
- Phenotype
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/metabolism*
- Zebrafish Proteins/physiology
- PubMed
- 24075420 Full text @ DNA Repair (Amst).
- CTD
- 24075420
This study is the first to validate the function of ogg1 during brain development using zebrafish embryos. Ogg1 was found to be highly expressed in the brain throughout early embryonic development, with particularly enrichment observed in the midbrain. The lack of ogg1 causes severe brain defects including changes in brain volume and integrity, destruction of the midbrain–hindbrain boundary, and balance and motor impairment, while overexpression of ogg1 can partially rescue these defects.
Multiple cellular and molecular events were involved in the manifestation of brain defects due primarily to the lack of ogg1. These included (1) increased apoptosis; (2) decreased proliferation; and (3) aberrant axon distribution and extension from the inner surface towards the outer layers. The results of a microarray analysis showed that the expression of genes involved in cell cycle checkpoint, apoptosis, and neurogenesis were significantly changed in response to ogg1 knockdown. Cmyb was the key downstream gene that responses to DNA damage caused by ogg1 deficiency. Notably, the recruitment of ogg1 mRNA can alleviate the effects on the brain due to neural DNA damage.
In summary, we introduce here that ogg1 is fundamentally required for protecting the developing brain, which may be helpful in understanding the aetiology of congenital brain deficits.