Checkpoint protein Rad9 plays an important role in nucleotide excision repair
Checkpoint protein Rad9 plays an important role in nucleotide excision repair
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检查点蛋白Rad9在核苷酸切除修复中发挥重要作用
DOI：
10.1016/j.dnarep.2013.01.006
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发表时间：
2013-04-01
期刊：
影响因子：
3.8
通讯作者：
Hang, Haiying
中科院分区：
文献类型：
--
作者：
Li, Tiepeng;Wang, Zhixin;Hang, Haiying
Rad 9是一个进化上保守的检查点基因，具有保护基因组完整性的多种功能，在同源重组修复、碱基切除修复和错配修复中发挥重要作用。然而，Rad 9是否对核苷酸切除修复有影响仍然未知。在这里，我们证明了Rad 9参与核苷酸切除修复，并且Rad 9的缺失导致哺乳动物细胞中UV衍生的光产物6-4PP（6，4嘧啶-嘧啶酮）和BPDE（抗苯并（a）芘-反式-7，8-二氢二醇-9，10-环氧化物）-DNA加合物的去除缺陷。我们还证明了Rad 9可以与XPC共定位，以响应局部UV照射。然而，我们的数据表明，Rad 9是不需要的核苷酸切除修复的光产物识别步骤。进一步的研究表明，Rad 9的减少降低了人类细胞中核苷酸切除修复因子DDB 2、XPC、DDB 1和XPB和DDB 2蛋白水平的基因的UV诱导转录。有趣的是，敲低DNA损伤识别复合物hHR 23 B的一个亚基会损害Rad 9加载到UV损伤的染色质上。基于这些结果，我们认为Rad 9通过包括维持人类细胞中DDB 2蛋白水平在内的机制在核苷酸切除修复中起重要作用。(C)2013爱思唯尔有限公司版权所有。
Rad9, an evolutionarily conserved checkpoint gene with multiple functions for preserving genomic integrity, has been shown to play important roles in homologous recombination repair, base excision repair and mismatch repair. However, whether Rad9 has an impact on nucleotide excision repair remains unknown. Here we demonstrated that Rad9 was involved in nucleotide excision repair and loss of Rad9 led to defective removal of the UV-derived photoproduct 6-4PP (6,4 pyrimidine-pyrimidone) and the BPDE (anti-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide)-DNA adducts in mammalian cells. We also demonstrated that Rad9 could co-localize with XPC in response to local UV irradiation. However, our data showed that Rad9 was not required for the photoproducts recognition step of nucleotide excision repair. Further investigation revealed that reduction of Rad9 reduced the UV-induced transcription of the genes of the nucleotide excision repair factors DDB2, XPC, DDB1 and XPB and DDB2 protein levels in human cells. Interestingly, knockdown of one subunit of DNA damage recognition complex, hHR23B impaired Rad9-loading onto UV-damaged chromatin. Based on these results, we suggest that Rad9 plays an important role in nucleotide excision repair through mechanisms including maintaining DDB2 protein level in human cells. (C) 2013 Elsevier B.V. All rights reserved.