Centrin 2 stimulates nucleotide excision repair by interacting with xeroderma pigmentosum group C protein
Centrin 2 stimulates nucleotide excision repair by interacting with xeroderma pigmentosum group C protein
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DOI：
10.1128/mcb.25.13.5664-5674.2005
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发表时间：
2005-07-01
影响因子：
5.3
通讯作者：
Hanaoka, F
中科院分区：
文献类型：
--
作者：
Nishi, R;Okuda, Y;Hanaoka, F
着色性干皮病C组（XPC）蛋白在全基因组核苷酸切除修复（NER）的DNA损伤识别中起着关键作用。该蛋白在体内形成异源三聚体复合物，涉及酿酒酵母Rad 23 p和中心蛋白2（一种中心体蛋白）的两种人类同源物之一。由于中心蛋白2在无细胞NER反应中起重要作用，因此其在NER中的作用尚不清楚。一系列截短的XPC蛋白的结合实验允许的中心蛋白2结合域被映射到一个假定的α-螺旋区域附近的C末端，在这个域中的三个氨基酸取代废除与中心蛋白2的相互作用。稳定表达突变XPC蛋白的人细胞系表现出全局基因组NER活性的显著降低。此外，中心蛋白2增强了XPC的无细胞NER双切割和破坏DNA结合活性，这可能需要XPC和中心蛋白2之间的物理相互作用。这些结果揭示了中心蛋白2在NER中的一种新的重要功能，即XPC对损伤识别的增强作用。
Xeroderma pigmentosum group C (XPC) protein plays a key role in DNA damage recognition in global genome nucleotide excision repair (NER). The protein forms in vivo a heterotrimeric complex involving one of the two human homologs of Saccharomyces cerevisiae Rad23p and centrin 2, a centrosomal protein. Because centrin 2 is dispensable for the cell-free NER reaction, its role in NER has been unclear. Binding experiments with a series of truncated XPC proteins allowed the centrin 2 binding domain to be mapped to a presumed alpha-helical region near the C terminus, and three amino acid substitutions in this domain abrogated interaction with centrin 2. Human cell lines stably expressing the mutant XPC protein exhibited a significant reduction in global genome NER activity. Furthermore, centrin 2 enhanced the cell-free NER dual incision and damaged DNA binding activities of XPC, which likely require physical interaction between XPC and centrin 2. These results reveal a novel vital function for centrin 2 in NER, the potentiation of damage recognition by XPC.