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The oligonucleotide/oligosaccharide-binding fold motif is a poly(ADP-ribose)-binding domain that mediates DNA damage response

机译:寡核苷酸/寡糖结合折叠基序是介导DNA损伤反应的聚(ADP-核糖)结合域

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摘要

Oligonucleotide/oligosaccharide-binding (OB) fold is a ssDNA or RNA binding motif in prokaryotes and eukaryotes. Unexpectedly, we found that the OB fold of human ssDNA-binding protein 1 (hSSB1) is a poly(ADP ribose) (PAR) binding domain. hSSB1 exhibits high-affinity binding to PAR and recognizes iso-ADP ribose (ADPR), the linkage between two ADPR units. This interaction between PAR and hSSB1 mediates the early recruitment of hSSB1 to the sites of DNA damage. Mutations in the OB fold of hSSB1 that disrupt PAR binding abolish the relocation of hSSB1 to the sites of DNA damage. Moreover, PAR-mediated recruitment of hSSB1 is important for early DNA damage repair. We have screened other OB folds and found that several other OB folds also recognize PAR. Taken together, our study reveals a PAR-binding domain that mediates DNA damage repair.
机译:寡核苷酸/寡糖结合(OB)折叠是原核生物和真核生物中的ssDNA或RNA结合基序。出乎意料的是,我们发现人ssDNA结合蛋白1(hSSB1)的OB折叠是一个poly(ADP核糖)(PAR)结合域。 hSSB1表现出与PAR的高亲和力结合,并识别iso-ADP核糖(ADPR),即两个ADPR单元之间的连接。 PAR和hSSB1之间的这种相互作用介导了hSSB1早期募集到DNA损伤部位。 hSSB1的OB折叠中破坏PAR结合的突变消除了hSSB1向DNA损伤位点的重新定位。此外,PAR介导的hSSB1募集对于早期DNA损伤修复非常重要。我们筛选了其他OB折叠,发现其他几个OB折叠也可以识别PAR。综上所述,我们的研究揭示了介导DNA损伤修复的PAR结合域。

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