Functional Role of N-Terminal Extension of Human AP Endonuclease 1 In Coordination of Base Excision DNA Repair via Protein-Protein Interactions
Autor: | N. A. Moor, Olga I. Lavrik, Inna A. Vasil'eva |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
DNA Repair DNA polymerase DNA repair Poly (ADP-Ribose) Polymerase-1 protein–protein interactions base excision repair Catalysis Fluorescence Article AP endonuclease lcsh:Chemistry Inorganic Chemistry 03 medical and health sciences XRCC1 Protein Domains DNA-(Apurinic or Apyrimidinic Site) Lyase Humans AP site Protein Interaction Maps Physical and Theoretical Chemistry lcsh:QH301-705.5 Molecular Biology Spectroscopy Polymerase DNA Polymerase beta Binding Sites 030102 biochemistry & molecular biology biology Chemistry Organic Chemistry APE1 multifunctional disordered protein fluorescence techniques General Medicine Base excision repair DNA Computer Science Applications Cell biology 030104 developmental biology X-ray Repair Cross Complementing Protein 1 lcsh:Biology (General) lcsh:QD1-999 Gene Expression Regulation DNA glycosylase Mutation biology.protein Protein Binding |
Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences; Volume 21; Issue 9; Pages: 3122 International Journal of Molecular Sciences, Vol 21, Iss 3122, p 3122 (2020) |
ISSN: | 1422-0067 |
Popis: | Human apurinic/apyrimidinic endonuclease 1 (APE1) has multiple functions in base excision DNA repair (BER) and other cellular processes. Its eukaryote-specific N-terminal extension plays diverse regulatory roles in interaction with different partners. Here, we explored its involvement in interaction with canonical BER proteins. Using fluorescence based-techniques, we compared binding affinities of the full-length and N-terminally truncated forms of APE1 (APE1NΔ35 and APE1NΔ61) for functionally and structurally different DNA polymerase β (Polβ), X-ray repair cross-complementing protein 1 (XRCC1), and poly(adenosine diphosphate (ADP)-ribose) polymerase 1 (PARP1), in the absence and presence of model DNA intermediates. Influence of the N-terminal truncation on binding the AP site-containing DNA was additionally explored. These data suggest that the interaction domain for proteins is basically formed by the conserved catalytic core of APE1. The N-terminal extension being capable of dynamically interacting with the protein and DNA partners is mostly responsible for DNA-dependent modulation of protein–protein interactions. Polβ, XRCC1, and PARP1 were shown to more efficiently regulate the endonuclease activity of the full-length protein than that of APE1NΔ61, further suggesting contribution of the N-terminal extension to BER coordination. Our results advance the understanding of functional roles of eukaryote-specific protein extensions in highly coordinated BER processes. |
Databáze: | OpenAIRE |
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