Nucleolin inhibits G4 oligonucleotide unwinding by Werner helicase.
Nucleolin inhibits G4 oligonucleotide unwinding by Werner helicase.
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DOI：
10.1371/journal.pone.0035229
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Bohr VA
中科院分区：
文献类型：
--
作者：
Indig FE;Rybanska I;Karmakar P;Devulapalli C;Fu H;Carrier F;Bohr VA
The Werner protein (WRNp), a member of the RecQ helicase family, is strongly associated with the nucleolus, as is nucleolin (NCL), an important nucleolar constituent protein. Both WRNp and NCL respond to the effects of DNA damaging agents. Therefore, we have investigated if these nuclear proteins interact and if this interaction has a possible functional significance in DNA damage repair. Here we report that WRNp interacts with the RNA-binding protein, NCL, based on immunoprecipitation, immunofluorescent co-localization in live and fixed cells, and direct binding of purified WRNp to nucleolin. We also map the binding region to the C-terminal domains of both proteins. Furthermore, treatment of U2OS cells with 15 µM of the Topoisomerase I inhibitor, camptothecin, causes the dissociation of the nucleolin-Werner complex in the nucleolus, followed by partial re-association in the nucleoplasm. Other DNA damaging agents, such as hydroxyurea, Mitomycin C, and aphidicolin do not have these effects. Nucleolin or its C-terminal fragment affected the helicase, but not the exonuclease activity of WRNp, by inhibiting WRN unwinding of G4 tetraplex DNA structures, as seen in activity assays and electrophoretic mobility shift assays (EMSA). These data suggest that nucleolin may regulate G4 DNA unwinding by WRNp, possibly in response to certain DNA damaging agents. We postulate that the NCL-WRNp complex may contain an inactive form of WRNp, which is released from the nucleolus upon DNA damage. Then, when required, WRNp is released from inhibition and can participate in the DNA repair processes.
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影响因子：
5.3
作者：
Daniely, Y;Dimitrova, DD;Borowiec, JA
通讯作者：
Borowiec, JA
影响因子：
9.2
作者：
Andersen, JS;Lyon, CE;Lamond, AI
通讯作者：
Lamond, AI
DOI：
10.1073/pnas.94.8.3605
发表时间：
1997-04-15
影响因子：
11.1
作者：
Hanakahi, LA;Dempsey, LA;Maizels, N
通讯作者：
Maizels, N
影响因子：
4.8
作者：
Dempsey, LA;Sun, H;Maizels, N
通讯作者：
Maizels, N
影响因子：
5.3
作者：
Kim, K;Dimitrova, DD;Borowiec, JA
通讯作者：
Borowiec, JA