Novel mechanisms for the removal of strong replication-blocking HMCES- and thiazolidine-DNA adducts in humans.

ABSTRACT: Apurinic/apyrimidinic (AP) sites are DNA lesions created under normal growth conditions that result in cytotoxicity, replication-blocks, and mutations. AP sites are susceptible to β-elimination and are liable to be converted to DNA strand breaks. HMCES (5-hydroxymethylcytosine binding, ES cell specific) protein interacts with AP sites in single stranded (ss) DNA exposed at DNA replication forks to generate a stable thiazolidine protein-DNA crosslink and protect cells against AP site toxicity. The crosslinked HMCES is resolved by proteasome-mediated degradation; however, it is unclear how HMCES-crosslinked ssDNA and the resulting proteasome-degraded HMCES adducts are processed and repaired. Here, we describe methods for the preparation of thiazolidine adduct-containing oligonucleotides and

SUBMITTER: Sugimoto Y 

PROVIDER: S-EPMC10250235 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature