Department of Chemistry, University of California, One Shields Avenue, Davis, CA 95616, USA.
Proc Natl Acad Sci U S A. 2010 Nov 30;107(48):20715-9. doi: 10.1073/pnas.1009231107. Epub 2010 Nov 10.
Editing of the pre-mRNA for the DNA repair enzyme NEIL1 causes a lysine to arginine change in the lesion recognition loop of the protein. The two forms of NEIL1 are shown here to have distinct enzymatic properties. The edited form removes thymine glycol from duplex DNA 30 times more slowly than the form encoded in the genome, whereas editing enhances repair of the guanidinohydantoin lesion by NEIL1. In addition, we show that the NEIL1 recoding site is a preferred editing site for the RNA editing adenosine deaminase ADAR1. The edited adenosine resides in an A-C mismatch in a hairpin stem formed by pairing of exon 6 to the immediate upstream intron 5 sequence. As expected for an ADAR1 site, editing at this position is increased in human cells treated with interferon α. These results suggest a unique regulatory mechanism for DNA repair and extend our understanding of the impact of RNA editing.
编辑 DNA 修复酶 NEIL1 的前体 mRNA 会导致蛋白质中损伤识别环中的赖氨酸突变为精氨酸。如图所示，这两种形式的 NEIL1 具有不同的酶学特性。编辑后的形式从双链 DNA 中去除胸腺嘧啶二醇的速度比基因组编码的形式慢 30 倍，而编辑则增强了 NEIL1 对鸟嘌呤脒基乙内酰脲损伤的修复。此外，我们还表明，NEIL1 重编码位点是 RNA 编辑腺苷脱氨酶 ADAR1 的首选编辑位点。编辑后的腺苷位于由外显子 6 与紧邻的上游内含子 5 序列配对形成的发夹茎中的 A-C 错配中。正如 ADAR1 位点所预期的那样，用干扰素 α 处理人细胞时，该位置的编辑增加。这些结果为 DNA 修复提供了一种独特的调控机制，并扩展了我们对 RNA 编辑影响的理解。
