期刊
BIOCHEMICAL JOURNAL
卷 452, 期 -, 页码 545-557出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20121277
关键词
apurinic/apyrimidinic endonuclease 1 (APE1); nucleophosmin (NPM1); protein-DNA interaction; protein-protein interaction; phylogenesis
资金
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [IG10269]
- Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR) [FIRB_RBRN07BMCT, PRIN2008_CCPKRP_003]
The hAPE1 (human apurinic/apyrimidinic endonuclease 1) is an essential enzyme, being the main abasic endonuclease in higher eukaryotes. However, there is strong evidence to show that hAPE1 can directly bind specific gene promoters, thus modulating their transcriptional activity, even in the absence of specific DNA damage. Recent findings, moreover, suggest a role for hAPE1 in RNA processing, which is modulated by the interaction with NPM1 (nucleophosmin). Independent domains account for many activities of hAPE1; however, whereas the endonuclease and the redox-active portions of the protein are well characterized, a better understanding of the role of the unstructured N-terminal region is needed. In the present study, we characterized the requirements for the interaction of hAPE1 with NPM1 and undamaged nucleic acids. We show that DNA/RNA secondary structure has an impact on hAPE1 binding in the absence of damage. Biochemical studies, using the isolated N-terminal region of the protein, reveal that the hAPE1 N-terminal domain represents an evolutionary gain of function, since its composition affects the protein's stability and ability to interact with both nucleic acids and NPM1. Although required, however, this region is not sufficient itself to stably interact with DNA or NPM1.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据