RGD Reference Report - Ischemic preconditioning induces XRCC1, DNA polymerase-beta, and DNA ligase III and correlates with enhanced base excision repair. - Rat Genome Database

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Ischemic preconditioning induces XRCC1, DNA polymerase-beta, and DNA ligase III and correlates with enhanced base excision repair.

Authors: Li, N  Wu, H  Yang, S  Chen, D 
Citation: Li N, etal., DNA Repair (Amst). 2007 Sep 1;6(9):1297-306. Epub 2007 Apr 6.
RGD ID: 2302580
Pubmed: (View Article at PubMed) PMID:17412650
DOI: Full-text: DOI:10.1016/j.dnarep.2007.02.027

Neuronal protection induced by ischemic preconditioning has an important role in the reduction of stroke volume and attenuation of neuronal cell death. Ischemic injury is associated with increased oxidative DNA damage, and failure to efficiently repair these oxidatively damaged lesions results in the accumulation of mutations and neuronal cell death. Although the effects of ischemic tolerance can have profound implications, the precise mechanisms mediating this phenomenon remain unclear. The base excision repair (BER) pathway has a major role in the repair of oxidative DNA base damage after ischemic injury. Using a rat model of ischemic preconditioning, we now report that the neuronal protection observed after induction of ischemic tolerance is associated with increased BER. In situ detection of single-strand breaks and apurinic/apyrimidinic sites reduced to baseline levels after reperfusion following ischemic preconditioning. By contrast, no change was seen in the quantity of in situ lesions after reperfusion in non-ischemic preconditioned brain. Induction of the BER proteins XRCC1, DNA polymerase-beta, and DNA ligase III was seen after reperfusion in ischemically conditioned brain. Moreover, an increase in binding between XRCC1 and DNA polymerase-beta was seen under these conditions, as might be expected during formation of functional BER complexes. Using in vitro BER oligonucleotides, we directly demonstrated an increase in total BER capacity of nuclear extracts prepared from ischemic-conditioned brain after reperfusion compared with sham-operated brain. These findings provide direct evidence that increased BER is associated with the neuroprotection induced after ischemic preconditioning, and provides important new mechanistic insight into the important biologic pathways that protect neurons against irreversible ischemic injury.


Disease Annotations    
Reperfusion Injury  (IEP,ISO)

Gene Ontology Annotations    

Biological Process

Cellular Component
nucleus  (IDA)

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Lig3  (DNA ligase 3)
Polb  (DNA polymerase beta)
Xrcc1  (X-ray repair cross complementing 1)

Genes (Mus musculus)
Lig3  (ligase III, DNA, ATP-dependent)
Polb  (polymerase (DNA directed), beta)
Xrcc1  (X-ray repair complementing defective repair in Chinese hamster cells 1)

Genes (Homo sapiens)
LIG3  (DNA ligase 3)
POLB  (DNA polymerase beta)
XRCC1  (X-ray repair cross complementing 1)

Additional Information