文章基本信息

标题：Investigation of the core binding regions of human Werner syndrome and Fanconi anemia group J helicases on replication protein A
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作者：Gyuho Yeom ; Jinwoo Kim ; Chin-Ju Park 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2019
卷号：9
期号：1
页码：1-10
DOI：10.1038/s41598-019-50502-8
出版社：Springer Nature
摘要：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.