Role of the unstructured N-terminal domain of the human Apurinic/Apyrimidinic Endonuclease 1 (hAPE1) in the modulation of its interaction with nucleic acids and Nucleophosmin (NPM1)

The human Apurinic/apyrimidinic endonuclease 1 (hAPE1) is an essential enzyme, being the main abasic endonuclease in higher eukaryotes. However, many evidences 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 Nucleophosmin (NPM1). Independent domains account for many activities of hAPE1; however, while 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. Here, we characterized the requirements for the interaction of hAPE1 with NPM1 and with 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, per se, to stably interact with DNA or NPM1.

Source: BJ Gene - April 2, 2013 Category: Biochemistry Authors: M Poletto, C Vascotto, P L. Scognamiglio, L Lirussi, D Marasco, G Tell Tags: BJ Gene Source Type: research