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Partial loss of the DNA repair scaffolding protein, Xrcc1, results in increased brain damage and reduced recovery from ischemic stroke in mice
- Publication Year :
- 2015
- Publisher :
- Zenodo, 2015.
-
Abstract
- Oxidative DNA damage is mainly repaired by base excision repair (BER). Previously, our laboratory showed that mice lacking the BER glycosylases 8-oxoguanine glycosylase 1 (Ogg1) or nei endonuclease VIII-like 1 (Neil1) recover more poorly from focal ischemic stroke than wild-type mice. Here, a mouse model was used to investigate whether loss of 1 of the 2 alleles of X-ray repair cross-complementing protein 1 (Xrcc1), which encodes a nonenzymatic scaffold protein required for BER, alters recovery from stroke. Ischemia and reperfusion caused higher brain damage and lower functional recovery in Xrcc1(+/-) mice than in wild-type mice. Additionally, a greater percentage of Xrcc1(+/-) mice died as a result of the stroke. Brain samples from human individuals who died of stroke and individuals who died of non-neurological causes were assayed for various steps of BER. Significant losses of thymine glycol incision, abasic endonuclease incision, and single nucleotide incorporation activities were identified, as well as lower expression of XRCC1 and NEIL1 proteins in stroke brains compared with controls. Together, these results suggest that impaired BER is a risk factor in ischemic brain injury and contributes to its recovery.
- Subjects :
- Male
Aging
medicine.medical_specialty
DNA Repair
DNA repair
Ischemia
NEIL1
Gene Expression
Loss of Heterozygosity
Brain damage
Biology
Article
DNA Glycosylases
Mice
XRCC1
Risk Factors
Internal medicine
medicine
Animals
Humans
Hypoxia, Brain
Stroke
Nucleotides
General Neuroscience
Base excision repair
Endonucleases
medicine.disease
Surgery
DNA-Binding Proteins
Disease Models, Animal
X-ray Repair Cross Complementing Protein 1
Endocrinology
DNA glycosylase
Neurology (clinical)
Geriatrics and Gerontology
medicine.symptom
Thymine
DNA Damage
Developmental Biology
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....98ba7dd8a77e71c1ffdbd95d21ca0201