Eukaryotic genomic DNA is packed into chromatin, whose fundamental structural unit is the nucleosome. As DNA-histone protein complexes, nucleosomes show different properties toward exogenous and endogenous DNA-damagin...Eukaryotic genomic DNA is packed into chromatin, whose fundamental structural unit is the nucleosome. As DNA-histone protein complexes, nucleosomes show different properties toward exogenous and endogenous DNA-damaging agents. This review summarizes nucleosome DNA damage due to different sources, including alkylating agents, radicals, UV radiation and reactive DNA damage intermediates. In most cases, the histone core protects the associated DNA against damage via its structure and/or scavenging of damaging agents. In contrast, histones react with damaged DNA and, in some instances, catalyze DNA damage in the nucleosome. The biological consequence of nucleosome DNA damage and future prospects in this field are briefly discussed.展开更多
Biological application of conjugates derived from oligonucleotides and quinone methides have pre- viously been limited by the slow exchange of their covalent self-adducts and subsequent alkylation of target nucleic ac...Biological application of conjugates derived from oligonucleotides and quinone methides have pre- viously been limited by the slow exchange of their covalent self-adducts and subsequent alkylation of target nucleic acids. To enhance the rates of these processes, a new quinone methide precursor with an electron donating substituent has been prepared. Additionally, this substi- tuent has been placed para to the nascent exo-methylene group of the quinone methide for maximum effect. A conjugate made from this precursor and a 5＇-aminohex- yloligonucleotide accelerates formation of its reversible self-adduct and alkylation of its complementary DNA as predicted from prior model studies.展开更多
基金supported by the National Natural Science Foundation of China(21572109,21877064,21740002)the National Key R&D Program of China(2017YFD0200501)
文摘Eukaryotic genomic DNA is packed into chromatin, whose fundamental structural unit is the nucleosome. As DNA-histone protein complexes, nucleosomes show different properties toward exogenous and endogenous DNA-damaging agents. This review summarizes nucleosome DNA damage due to different sources, including alkylating agents, radicals, UV radiation and reactive DNA damage intermediates. In most cases, the histone core protects the associated DNA against damage via its structure and/or scavenging of damaging agents. In contrast, histones react with damaged DNA and, in some instances, catalyze DNA damage in the nucleosome. The biological consequence of nucleosome DNA damage and future prospects in this field are briefly discussed.
文摘Biological application of conjugates derived from oligonucleotides and quinone methides have pre- viously been limited by the slow exchange of their covalent self-adducts and subsequent alkylation of target nucleic acids. To enhance the rates of these processes, a new quinone methide precursor with an electron donating substituent has been prepared. Additionally, this substi- tuent has been placed para to the nascent exo-methylene group of the quinone methide for maximum effect. A conjugate made from this precursor and a 5＇-aminohex- yloligonucleotide accelerates formation of its reversible self-adduct and alkylation of its complementary DNA as predicted from prior model studies.
