Synthesis of cross-linked DNA containing oxidized abasic site analogues.

ABSTRACT: DNA interstrand cross-links are an important family of DNA damage that block replication and transcription. Recently, it was discovered that oxidized abasic sites react with the opposing strand of DNA to produce interstrand cross-links. Some of the cross-links between 2'-deoxyadenosine and the oxidized abasic sites, 5'-(2-phosphoryl-1,4-dioxobutane) (DOB) and the C4-hydroxylated abasic site (C4-AP), are formed reversibly. Chemical instability hinders biochemical, structural, and physicochemical characterization of these cross-linked duplexes. To overcome these limitations, we developed methods for preparing stabilized analogues of DOB and C4-AP cross-links via solid-phase oligonucleotide synthesis. Oligonucleotides of any sequence are attainable by synthesizing phosphoramidites in which th

SUBMITTER: Ghosh S 

PROVIDER: S-EPMC4084848 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature