A copper(ii) peptide helicate selectively cleaves DNA replication foci in mammalian cells.

ABSTRACT: The use of copper-based artificial nucleases as potential anticancer agents has been hampered by their poor selectivity in the oxidative DNA cleavage process. An alternative strategy to solve this problem is to design systems capable of selectively damaging noncanonical DNA structures that play crucial roles in the cell cycle. We designed an oligocationic Cu^II peptide helicate that selectively binds and cleaves DNA three-way junctions (3WJs) and induces oxidative DNA damage via a ROS-mediated pathway both in vitro and in cellulo, specifically at DNA replication foci of the cell nucleus, where this DNA structure is transiently generated. To our knowledge, this is the first example of a targeted chemical nuclease that can discriminate with high selectivity 3WJ

SUBMITTER: Alcalde-Ordonez A 

PROVIDER: S-EPMC10718067 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature