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: PMID:17412650   (View Abstract at PubMed)
DOI: DOI:10.1016/j.dnarep.2007.02.027   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
LIG3Humanmiddle cerebral artery infarction  ISOLig3 (Rattus norvegicus)associated with transient cerebral ischemia and protein:increased expression:brainRGD 
Lig3Ratmiddle cerebral artery infarction  IEP associated with transient cerebral ischemia and protein:increased expression:brainRGD 
Lig3Mousemiddle cerebral artery infarction  ISOLig3 (Rattus norvegicus)associated with transient cerebral ischemia and protein:increased expression:brainRGD 
POLBHumanmiddle cerebral artery infarction  ISOPolb (Rattus norvegicus)associated with transient cerebral ischemia and protein:increased expression:brainRGD 
PolbRatmiddle cerebral artery infarction  IEP associated with transient cerebral ischemia and protein:increased expression:brainRGD 
PolbMousemiddle cerebral artery infarction  ISOPolb (Rattus norvegicus)associated with transient cerebral ischemia and protein:increased expression:brainRGD 
XRCC1Humanmiddle cerebral artery infarction  ISOXrcc1 (Rattus norvegicus)associated with transient cerebral ischemia and protein:increased expression:brainRGD 
Xrcc1Ratmiddle cerebral artery infarction  IEP associated with transient cerebral ischemia and protein:increased expression:brainRGD 
Xrcc1Mousemiddle cerebral artery infarction  ISOXrcc1 (Rattus norvegicus)associated with transient cerebral ischemia and protein:increased expression:brainRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Xrcc1Ratbase-excision repair  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Lig3RatDNA ligase activity  IDA  RGD 
PolbRatDNA-directed DNA polymerase activity  IDA  RGD 
PolbRatprotein binding  IPIXrcc1 (Rattus norvegicus) RGD 
Xrcc1Ratprotein binding  IPIPolb (Rattus norvegicus) RGD 

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