Investigation of the core binding regions of human Werner syndrome and Fanconi anemia group J helicases on replication protein A

Werner syndrome protein (WRN) and Fanconi anemia group J protein (FANCJ) are human DNA helicases that contribute to genome maintenance. They interact with replication protein A (RPA), and these interactions dramatically enhance the unwinding activities of both helicases. Even though the interplay be...

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Bibliographic Details
Published in:Scientific reports 2019-09, Vol.9 (1), p.14016-10, Article 14016
Main Authors: Yeom, Gyuho, Kim, Jinwoo, Park, Chin-Ju
Format: Article
Language:English
Subjects:
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Anemia
Anisotropy
Binding Sites
Cancer
Chemoresistance
Deoxyribonucleic acid
DNA
DNA damage
DNA helicase
Fanconi Anemia - enzymology
Fanconi Anemia Complementation Group Proteins - metabolism
Fanconi syndrome
Fluorescence polarization
Genomes
Humanities and Social Sciences
Humans
Interfaces
J protein
Magnetic Resonance Spectroscopy
multidisciplinary
Protein interaction
Proteins
Replication protein A
Replication Protein A - metabolism
RNA Helicases - metabolism
Science
Science (multidisciplinary)
Unwinding
Werner Syndrome - enzymology
Werner Syndrome Helicase - metabolism
Werner's syndrome
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Summary:Werner syndrome protein (WRN) and Fanconi anemia group J protein (FANCJ) are human DNA helicases that contribute to genome maintenance. They interact with replication protein A (RPA), and these interactions dramatically enhance the unwinding activities of both helicases. Even though the interplay between these helicases and RPA is particularly important in the chemoresistance pathway of cancer cells, the precise binding regions, interfaces, and properties have not yet been characterized. Here we present systematic NMR analyses and fluorescence polarization anisotropy assays of both helicase-RPA interactions for defining core binding regions and binding affinities. Our results showed that two acidic repeats of human WRN bind to RPA70N and RPA70A. For FANCJ, the acidic-rich sequence in the C-terminal domain is the binding region for RPA70N. Our results suggest that each helicase interaction has unique features, although they both fit an acidic peptide into a basic cleft for RPA binding. Our findings shed light on the protein interactions involved in overcoming the DNA-damaging agents employed in the treatment of cancer and thus potentially provide insight into enhancing the efficacy of cancer therapy.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-50502-8