Human ribosomal protein S3 interacts with DNA base excision repair proteins hAPE/Ref-1 and hOGG1
Human ribosomal protein S3 interacts with DNA base excision repair proteins hAPE/Ref-1 and hOGG1
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DOI：
10.1021/bi049234b
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发表时间：
2004-11-09
期刊：
影响因子：
2.9
通讯作者：
Deutsch, WA
中科院分区：
文献类型：
--
作者：
Hegde, V;Wang, M;Deutsch, WA
人核糖体蛋白S3（hS 3）具有相关的活动，建议替代作用以外的参与蛋白质翻译。例如，它能够通过β-消除反应切割脱嘌呤/脱嘧啶（AP）DNA，这是在着色性干皮病D组成纤维细胞的部分纯化提取物中缺失的活性。在最近的一项研究中，我们通过表面等离子体共振（SPR）表明，hS 3也具有非常高的表观结合亲和力的7，8-二氢-8-氧代鸟嘌呤（8-oxoG）和AP位点的DNA。使用相同的SPR技术，这里显示hS 3与人碱基切除修复（BER）酶N-糖基化酶/AP裂解酶OGG 1和APE/Ref-1积极相互作用。使用允许检测8-oxoG修复的DNA底物，我们还表明hOGG 1 N-糖基化酶活性在hS 3存在下变得越来越稳健。发现人S3与hOGG 1和APE/Ref-1两者共免疫沉淀，表明这些蛋白质彼此物理相互作用。这些结果提出了hS 3不仅作为核糖体蛋白发挥功能，而且还可能影响DNA损伤位点的修复活性的可能性。
The human ribosomal protein S3 (hS3) possesses associated activities that suggest alternative roles beyond its participation in protein translation. For example, it is capable of cleaving apurinic/ apyrimidinic (AP) DNA via a beta-elimination reaction, an activity that is missing in partially purified extracts of xeroderma pigmentosum group-D fibroblasts. In a recent study, we showed by surface plasmon resonance (SPR) that hS3 also has a very high apparent binding affinity for 7,8-dihydro-8-oxoguanine (8-oxoG) and AP sites in DNA. Using the same SPR technology, it is shown here that hS3 positively interacts with the human base excision repair (BER) enzymes N-glycosylase/AP lyase OGG1 and APE/Ref-1. Using a DNA substrate that allows for the detection of 8-oxoG repair, we also show that hOGG1 N-glycosylase activity becomes increasingly more robust in the presence of hS3. Human S3 was found to co-immunoprecipitate with both hOGG1 and APE/Ref-1, indicating that these proteins physically interact with one another. These results raise the possibility that hS3 not only functions as a ribosomal protein but, in addition, may influence repair activities at sites of DNA damage.