Functional role of N-terminal extension of human ap endonuclease 1 in coordination of base excision dna repair via protein–protein interactions

Nina Moor, Inna Vasil’eva, Olga Lavrik

Результат исследования: Научные публикации в периодических изданияхстатья

1 Цитирования (Scopus)

Аннотация

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 (APE1N∆35 and APE1N∆61) 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 APE1N∆61, 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.

Язык оригиналаанглийский
Номер статьи3122
Число страниц18
ЖурналInternational Journal of Molecular Sciences
Том21
Номер выпуска9
DOI
СостояниеОпубликовано - 28 апр 2020

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