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Ganoboninketal C from Ganoderma boninense improves the efficacy of CDDP-based chemotherapy through inhibiting translesion dna synthesis

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Food Science and Human Wellness 2024年第5期13卷 2982-2992页

作者： Xiaolu Ma Fei Yang Ke Ma Hongyan Shen Junjie Han Kai Wang Yeran Yang Jiawei Zhu Ruiyuan An Qilin Wang Tie-Shan Tang Bo Zhou Hongwei Liu Caixia Guo College of Biomedical Engineering Taiyuan University of TechnologyTaiyuan 030024China CAS Key Laboratory of Genomics and Precision Medicine Beijing Institute of Genomics/China National Center for BioinformationUniversity of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100101China State Key Laboratory of Membrane Biology Institute of ZoologyUniversity of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100101China Institute of Microbiology University of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China University of Chinese Academy of Sciences Chinese Academy of SciencesBeijing 100101China

translesion dna synthesis(TLS)can bypass dna lesions caused by chemotherapeutic drugs,which usually result in drug *** its key role in mutagenesis and cell survival after dna damage,inhibition of the TLS pathway has emerged as a potential target for improving the efficacy of dna-damaging agents such as cisplatin(CDDP),a widely used anticancer ***,few suitable natural TLS inhibitors have been ***,we found that a triterpenoid compound Ganoboninketal C(26-3)from Ganoderma boninense,a traditional Chinese medicine,can impair CDDP-induced TLS polymerase eta(Polη)focus formation,PCNA monoubiquitination as well as ***,26-3 can significantly sensitize tumor cells to CDDP killing and reduce the proportion of cancer stem cells in AGS and promote apoptosis after CDDP ***,26-3 can also sensitize tumor cells to Gefitinib ***,through RNA-seq analysis,we found that 26-3 could abrogate the CDDP-induced upregulation of Polηand PIDD(p53-induced protein with a death domain),2 known factors promoting TLS ***,we found that activating transcription factor 3 is a potential novel TLS *** together,we have identified a natural TLS inhibitor 26-3,which can be potentially used as an adjuvant to improve clinical efficacy.

关键词： Ganoderma boninense Ganoboninketal C Cisplatin chemotherapy translesion dna synthesis

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Structural insights into the assembly of human translesion polymerase complexes

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Protein & Cell 2012年第11期3卷 864-874页

作者： Wei Xie Xuan Yang Min Xu Tao Jiang National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of Sciences15 Datun RoadChaoyang DistrictBeijing 100101China The Graduate University of Chinese Academy of Sciences 19A Yuquan RoadShijingshan DistrictBeijing 100039China

In addition to dna repair pathways,cells utilize translesion dna synthesis(TLS)to bypass dna lesions during *** TLS,Y-family dna polymerase(Polη,Polκ,Polιand Rev1)inserts specific nucleotide opposite preferred dna lesions,and then Polζ consisting of two subunits,Rev3 and Rev7,carries out primer ***,we report the complex structures of Rev3-Rev7-Rev1^(CTD) and Rev3-Rev7-Rev1^(CTD)-Polκ^(RIR).These two structures demonstrate that Rev1^(CTD) contains separate binding sites for Polκand *** BIAcore experiments provide additional support for the notion that the interaction between Rev3 and Rev7 increases the affinity of Rev7 and *** also verified through FRET experiment that Rev1,Rev3,Rev7 and Polκ form a stable quaternary complex in vivo,thereby suggesting an efficient switching mechanism where the“inserter”polymerase can be immediately replaced by an“extender”polymerase within the same quaternary complex.

关键词： translesion dna synthesis Rev1 Polκ Polζ complex structure

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