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
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