Increased steady state mRNA levels of DNA-repair genes XRCC1, ERCC2 and ERCC3 in brain of patients with Down syndrome

Although deficient DNA-repair was proposed for neurodegenerative disorders including Down Syndrome (DS), repair genes for nucleotide excision repair o r X-ray repair have not been studied in brain yet. As one of the hypotheses for the pathogenesis of brain damage in DS is oxidative stress and cells o f patients with DS are more susceptible to ionizing irradiation, we decided to study ERCC2, ERCC3 and XRCC1, representatives of repair genes known to be involved in the repair of oxidative DNA-damage, mRNA steady state levels of ERCC2, ERCC3, XRCC1, a transcription activator (TAF-DBP) and an elongat ion factor (EF1A) were determined and normalized versus the housekeeping ge ne beta-actin in five individual brain regions of nine controls and nine DS patients. Although different in the individual regions, DNA-repair genes w ere consistently higher in temporal, parietal and occipital lobes of patien ts with DS accompanied by comparable changes of TFA-DBP and EF1A. Our resul ts are the first to describe DNA-repair gene patterns in human brain region s providing the basis for further studies in this area. We showed that DNA- repair genes ERCC2 and ERCC3 (excision-repair-cross-complementing-) for nuc leotide excision repair and XRCC1 (X-ray-repair-cross-complementing-) for X -ray-repair, were increased at the transcriptional level with the possible biological meaning that this increase may be compatible with permanent (oxi dative?) DNA damage.