5-Formyluracil targeted biochemical reactions with proteins inhibit DNA replication, induce mutations and interference gene expression in living cells

Covalent DNA-protein cross-links are toxic DNA lesions that interfere with essential biological processes, which can cause serious biological consequences, such as genomic instability and protein misexpression. 5-Formyluracil (5fU) as an important modification in DNA, which is mainly from oxidative damage, exists in a variety of cells and tissues. We have reported that 5fU mediated DNA-protein conjugates could exist in human cells [Zhou et al. CCS Chem. 2 (2020) 54-63]. We now aimed to explore its potential biological effects in vitro and in vivo. In this paper, we firstly reported that 5fU intermediated DNA-peptide or DNAprotein conjugates (both were called DPCs) could inhibit different polymerases bypass or cause mutations. Then we further investigated the functional impacts caused by 5fU-mediated DPCs, which appeared in different gene expression components [in the promoter sequence or 5'-untranslated regions (UTR)]. These results together may contribute to a broader understanding of DNA-protein interactions as well as the biological functions associated with 5fU. (C) 2021 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.