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首页> 外文期刊>Life sciences >Increased steady state mRNA levels of DNA-repair genes XRCC1, ERCC2 and ERCC3 in brain of patients with Down syndrome.
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Increased steady state mRNA levels of DNA-repair genes XRCC1, ERCC2 and ERCC3 in brain of patients with Down syndrome.

机译：唐氏综合症患者大脑中DNA修复基因XRCC1，ERCC2和ERCC3的稳态mRNA水平升高。

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Although deficient DNA-repair was proposed for neurodegenerative disorders including Down Syndrome (DS), repair genes for nucleotide excision repair or 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 of 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 elongation factor (EF1A) were determined and normalized versus the housekeeping gene beta-actin in five individual brain regions of nine controls and nine DS patients. Although different in the individual regions, DNA-repair genes were consistently higher in temporal, parietal and occipital lobes of patients with DS accompanied by comparable changes of TFA-DBP and EF1A. Our results are the first to describe DNA-repair gene 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 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 (oxidative?) DNA damage.
机译：尽管有人提议对包括唐氏综合症（DS）在内的神经退行性疾病进行DNA修复不足，但尚未在脑中研究核苷酸切除修复或X射线修复的修复基因。由于DS中脑损伤的发病机制的一种假设是氧化应激，DS患者的细胞更容易受到电离辐射的影响，我们决定研究ERCC2，ERCC3和XRCC1，这是已知参与修复的修复基因的代表DNA的氧化损伤。确定了ERCC2，ERCC3，XRCC1，转录激活因子（TAF-DBP）和延伸因子（EF1A）的mRNA稳态水平，并与9个对照和9个DS患者的5个单独脑区中的看家基因β-肌动蛋白进行了标准化。尽管个别区域不同，但DS患者的颞叶，顶叶和枕叶中的DNA修复基因始终较高，并伴有TFA-DBP和EF1A的可比变化。我们的结果首次描述了人脑区域的DNA修复基因模式，为该领域的进一步研究奠定了基础。我们发现，DNA修复基因ERCC2和ERCC3（核苷酸修复修复交叉互补）和XRCC1（X射线修复交叉互补）X射线修复在转录时均增加。可能具有生物学意义的水平，表明这种增加可能与永久性（氧化性）DNA损伤相容。

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