Human flap endonuclease 1 （FEN1） is a structure-specific, multi-functional endonuclease essential for DNA replication and repair. We and others have shown that during DNA replication, FEN1 processes Okazaki fragment...Human flap endonuclease 1 （FEN1） is a structure-specific, multi-functional endonuclease essential for DNA replication and repair. We and others have shown that during DNA replication, FEN1 processes Okazaki fragments via its interaction with the proliferating cell nuclear antigen （PCNA）. Alternatively, in response to DNA damage, FEN1 interacts with the PCNA-like Radg-Radl-Husl complex instead of PCNA to engage in DNA repair activities, such as homology-directed repair of stalled DNA replication forks. However, it is unclear how FEN1 is able to switch between these interactions and its roles in DNA replication and DNA repair. Here, we report that FEN1 undergoes SUMOylation by SUMO-1 in response to DNA replication fork-staUing agents, such as UV irradiation, hydroxyurea, and mitomycin C. This DNA damage-induced SUMO-1 modification promotes the interaction of FEN1 with the Radg-Rad1-Husl complex. Furthermore, we found that FEN1 mutations that prevent its SUMO-1 modification also impair its ability to interact with HUS1 and to rescue stalled replication forks. These impairments lead to the accumulation of DNA damage and heightened sensitivity to fork-staUing agents. Altogether, our findings suggest an important role of the SUMO-1 modification of FEN1 in regulating its roles in DNA replication and repair.展开更多
Ecological compensation plays an important role in implementing the social responsibility of infrastructure mega-projects. Based on the results of a field study, an in-depth interview, and archive data, this paper int...Ecological compensation plays an important role in implementing the social responsibility of infrastructure mega-projects. Based on the results of a field study, an in-depth interview, and archive data, this paper introduces the ecological compensation for Sousa chinensis(the Indo-Pacific humpbacked dolphin) during the construction of the Hong Kong-Zhuhai-Macao Bridge. It studies the concrete measures, decision-making processes,and organizational collaboration of the ecological compensation, using the method of a case study. The present study not only enriches our understanding of the ecological compensation practice during the construction of infrastructure mega-projects, but also extends the literature on the social responsibility of infrastructure mega-projects.This sheds light on the protection of the environment as well as biodiversity in the construction of future infrastructure mega-projects.展开更多
基金This work was supported by grants from the National Basic Research Program of China （2015CB910600）, the National Natural Science Foundation of China （31700688）, the National Key Research and Development Program of China （2017YFA0503900）, and the Natural Science Foundation of Zhejiang Province （LY16C050003） to Y.I.H. and H.X. A part of the work presented in the current article was supported by the National Institutes of Health grants ROICA073764 to B.H.S and R50CA211397 to L.Z.
文摘Human flap endonuclease 1 （FEN1） is a structure-specific, multi-functional endonuclease essential for DNA replication and repair. We and others have shown that during DNA replication, FEN1 processes Okazaki fragments via its interaction with the proliferating cell nuclear antigen （PCNA）. Alternatively, in response to DNA damage, FEN1 interacts with the PCNA-like Radg-Radl-Husl complex instead of PCNA to engage in DNA repair activities, such as homology-directed repair of stalled DNA replication forks. However, it is unclear how FEN1 is able to switch between these interactions and its roles in DNA replication and DNA repair. Here, we report that FEN1 undergoes SUMOylation by SUMO-1 in response to DNA replication fork-staUing agents, such as UV irradiation, hydroxyurea, and mitomycin C. This DNA damage-induced SUMO-1 modification promotes the interaction of FEN1 with the Radg-Rad1-Husl complex. Furthermore, we found that FEN1 mutations that prevent its SUMO-1 modification also impair its ability to interact with HUS1 and to rescue stalled replication forks. These impairments lead to the accumulation of DNA damage and heightened sensitivity to fork-staUing agents. Altogether, our findings suggest an important role of the SUMO-1 modification of FEN1 in regulating its roles in DNA replication and repair.
基金funded by National Natural Science Foundation of China:71390525,National Natural Science Foundation of China:71620107004Shanghai Excellent Academic Leaders Program:14XD1402200
文摘Ecological compensation plays an important role in implementing the social responsibility of infrastructure mega-projects. Based on the results of a field study, an in-depth interview, and archive data, this paper introduces the ecological compensation for Sousa chinensis(the Indo-Pacific humpbacked dolphin) during the construction of the Hong Kong-Zhuhai-Macao Bridge. It studies the concrete measures, decision-making processes,and organizational collaboration of the ecological compensation, using the method of a case study. The present study not only enriches our understanding of the ecological compensation practice during the construction of infrastructure mega-projects, but also extends the literature on the social responsibility of infrastructure mega-projects.This sheds light on the protection of the environment as well as biodiversity in the construction of future infrastructure mega-projects.
