Expression of DNA excision-repair-cross-complementing proteins p80 and p89 in brain of patients with Down Syndrome and Alzheimer's disease.
Although deficient DNA repair was proposed for neurodegenerative disorders including Down syndrome (DS), repair proteins for nucleotide excision repair have not been studied in brain yet. As one of the hypotheses for the pathogenesis of brain damage in DS and Alzheimer's disease (AD), is oxidative stress, and cells of patients with DS were shown to be more susceptible to ionizing irradiation. We decided to study expression of excision repair-cross-complementing (ERCC) gene products, proteins 80 and 89, representatives of repair genes known to be involved in the repair of different types of DNA damage. ERCC2-protein 80 kDa and ERCC3-protein p89 were determined in five individual brain regions of controls, aged DS and AD patients. Although different in the individual regions, DNA repair proteins were consistently higher in temporal and frontal lobes of patients with DS and higher in all brain regions of patients with AD. Our results are the first to describe DNA repair gene protein patterns in human brain regions providing the basis for further studies in this area. We showed that DNA repair genes ERCC2 and ERCC3 (excision-repair-cross-complementing) for nucleotide excision repair were increased at the protein level with the possible biological meaning that this increase may be compatible with and indicate ongoing (oxidative?) DNA damage.
Hermon
M
M
University of Vienna, Department of Pediatrics, Austria.
Cairns
N
N
Egly
J M
JM
Fery
A
A
Labudova
O
O
Lubec
G
G
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002531:Cerebellum / Q000737:chemistry; D002795:Choline O-Acetyltransferase / Q000032:analysis; D004249:DNA Damage; D004265:DNA Helicases; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D004314:Down Syndrome / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins; D005625:Frontal Lobe / Q000737:chemistry; D006801:Humans; D008875:Middle Aged; D009778:Occipital Lobe / Q000737:chemistry; D009928:Organ Specificity; D010296:Parietal Lobe / Q000737:chemistry; D011506:Proteins / Q000032:analysis / Q000235:genetics*; D012016:Reference Values; D013702:Temporal Lobe / Q000737:chemistry; D014157:Transcription Factors; D051759:Xeroderma Pigmentosum Group D Protein
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D011506:Proteins; D014157:Transcription Factors; C078672:hay protein, Drosophila; D002795:Choline O-Acetyltransferase; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human