Ku蛋白复合物参与DNA的核苷酸切除修复。

P Calsou, C Muller, P Frit, B Salles
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引用次数: 0

摘要

在鼠类电离辐射敏感(IRs)突变体互补组5 xrs6细胞系中,研究了核苷酸切除修复(NER)对UV-C (254 nm) DNA损伤的修复作用。xrs6细胞系显示dna末端结合蛋白复合物Ku存在缺陷,该蛋白参与IR引起的双链断裂(DSB)的修复。与IR敏感性一致,发现xrs6细胞系与亲本CHO-K1细胞系相比具有博来霉素敏感表型(因子> 8倍)。xrs6对UV-C光也表现出轻微的(因子2)但可重复的敏感性,而Ku dna末端结合活性的逆转细胞系xrs6rev显示出对IR和UV-C的敏感性恢复到亲本水平。这些细胞系的NER活性在核蛋白提取物中进行了体外测量,其中存在被NER修复的UV-C损伤的质粒DNA修复底物:与对照CHO-K1和xrs6rev细胞提取物相比,xrs6细胞提取物仅表现出55%的NER活性。这些结果表明,Ku DSB修复蛋白也参与了NER过程。
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Ku protein complex is involved in nucleotide excision repair of DNA.

The repair of UV-C (254 nm) DNA lesions by nucleotide excision repair (NER) has been studied in the rodent cell line xrs6 belonging to complementation group 5 of ionising radiation sensitive (IRs) mutants. xrs6 cell line shows a defect in the DNA-end binding protein complex Ku which is involved in the repair of double-strand breaks (DSB) due to IR. In agreement with IR sensitivity, a bleomycin sensitive phenotype of xrs6 cell line was found as compared to the parental CHO-K1 line (factor > 8 fold). xrs6 exhibited also a slight (factor 2) but reproducible sensitivity to UV-C-light, while a revertant cell line for Ku DNA-end binding activity, xrs6rev, showed a restoration of both IR and UV-C sensitivities to the parental level. The NER activity of these cell lines was measured in vitro in nuclear protein extracts in the presence of plasmid DNA repair substrate damaged with UV-C lesions repaired by NER: xrs6 cell extracts exhibited only 55% of NER activity as compared to the control CHO-K1 and xrs6rev cell extracts. These results indicate that the Ku DSB repair protein is involved also in the NER process.

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