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)
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)(572 views) Poletto M, Vascotto C, Scognamiglio PL, Lirussi L, Marasco D, Tell G
Keywords: Apurinic Apyrimidinic Endonuclease 1 (ape1), Nucleophosmin (npm1), Phylogenesis, Protein-Dna Interaction, Protein-Protein Interaction, Dna (apurinic Or Apyrimidinic Site) Lyase, Acetylation, Article, Binding Affinity, Dna Protein Complex, Dna Sequence, Dna Strand, Human, Human Cell, In Vitro Study, Nonhuman, Priority Journal, Protein Binding, Protein Conformation, Protein Cross Linking, Protein Protein Interaction, Protein Secondary Structure, Protein Stability, Signal Transduction, Stereospecificity, Ubiquitination, Amino Acid Sequence, Animals, Dna Damage, Dna-(apurinic Or Apyrimidinic Site) Lyase, Hela Cells, Molecular Sequence Data, Nuclear Proteins, Nucleic Acids, Sequence Homology, Zebrafish, Eukaryota,
Affiliations: *** IBB - CNR ***
Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy
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
References: Not available.
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 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 arewell 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. The Authors Journal compilation 2013 Biochemical Society
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)
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)