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.
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Research Article|
May 31 2013
Role of the unstructured N-terminal domain of the hAPE1 (human apurinic/apyrimidinic endonuclease 1) in the modulation of its interaction with nucleic acids and NPM1 (nucleophosmin)
Mattia Poletto;
Mattia Poletto
*Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy
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Carlo Vascotto;
Carlo Vascotto
*Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy
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Pasqualina L. Scognamiglio;
Pasqualina L. Scognamiglio
†Department of Pharmacy, CIRPEB (Centro Interuniversitario di Ricerca sui Peptidi Bioattivi), University of Naples ‘Federico II’, 80134 Naples, Italy
‡Institute of Biostructures and Bioimaging CNR, 80134 Naples, Italy
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Lisa Lirussi;
Lisa Lirussi
*Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy
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Daniela Marasco;
Daniela Marasco
†Department of Pharmacy, CIRPEB (Centro Interuniversitario di Ricerca sui Peptidi Bioattivi), University of Naples ‘Federico II’, 80134 Naples, Italy
‡Institute of Biostructures and Bioimaging CNR, 80134 Naples, Italy
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Gianluca Tell
Gianluca Tell
1
*Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy
1To whom correspondence should be addressed (email gianluca.tell@uniud.it).
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Publisher: Portland Press Ltd
Received:
August 14 2012
Revision Received:
March 28 2013
Accepted:
April 02 2013
Accepted Manuscript online:
April 02 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 452 (3): 545–557.
Article history
Received:
August 14 2012
Revision Received:
March 28 2013
Accepted:
April 02 2013
Accepted Manuscript online:
April 02 2013
Citation
Mattia Poletto, Carlo Vascotto, Pasqualina L. Scognamiglio, Lisa Lirussi, Daniela Marasco, Gianluca Tell; Role of the unstructured N-terminal domain of the hAPE1 (human apurinic/apyrimidinic endonuclease 1) in the modulation of its interaction with nucleic acids and NPM1 (nucleophosmin). Biochem J 15 June 2013; 452 (3): 545–557. doi: https://doi.org/10.1042/BJ20121277
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