Chemical Biology of Nucleosomes

【作者】 周传政；

【Author】 Chuanzheng Zhou;State Key of Laboratory of Element-organic Chemistry and Department of Chemical Biology,college of Chemistry,Nankai University;

【机构】 南开大学；

【摘要】 The nucleosome is the basic structural repeating unit of chromatin which consists of double-stranded DNA（dsDNA） wrapping around a histone octamer core.In the past several years,we designed experiments to gain insight on the mechanism of DNA damage and repair in nucleosomes.^[1] We demonstrated that histones participate in DNA damage in nucleosome through different manners.For instance,nucleophilic residues on histones,such as Lys and the N-terminal amino group,can react with electrophilic DNA damage intermediates to form DNA–protein cross-links.^[2,3] The bending structure of nucleosomal DNA inhibit the damage and repair of some DNA lesions in nucleosomes.^[4-8] On the other hand,based on the mechanistic studies of DNA damage in nucleosomes,we developed new tools for chemical protein modification and biomolecular interaction studies,^[9,10] which will be of interest in a wide range of biomedical applications,including identification of nucleic acid binding proteins,protein-protein interactions and preparation of antibody-drug conjugates.更多还原

【Abstract】 The nucleosome is the basic structural repeating unit of chromatin which consists of double-stranded DNA（dsDNA） wrapping around a histone octamer core.In the past several years,we designed experiments to gain insight on the mechanism of DNA damage and repair in nucleosomes.^[1] We demonstrated that histones participate in DNA damage in nucleosome through different manners.For instance,nucleophilic residues on histones,such as Lys and the N-terminal amino group,can react with electrophilic DNA damage intermediates to form DNA–protein cross-links.^[2,3] The bending structure of nucleosomal DNA inhibit the damage and repair of some DNA lesions in nucleosomes.^[4-8] On the other hand,based on the mechanistic studies of DNA damage in nucleosomes,we developed new tools for chemical protein modification and biomolecular interaction studies,^[9,10] which will be of interest in a wide range of biomedical applications,including identification of nucleic acid binding proteins,protein-protein interactions and preparation of antibody-drug conjugates.更多还原