Fig. 1: Overview of the DPC repair pathways, including nucleophagy.

Left: Reported mechanisms of DPC repair. (1) Proteolysis-dependent DPC repair, orchestrated by proteasome and proteases, acts on the protein level of DNA–protein crosslink. (2) Direct crosslink proteolysis resolves DNA–protein crosslinks on the level of crosslink/covalent bond. (3) In nuclease-dependent DPC repair, DPCs are processed by nucleotide excision repair and homologous recombination. Right: Nucleophagy — a novel mechanism of DPC repair. A type of selective autophagy, nucleophagy, is orchestrated by TEX264. Selective autophagy processes nuclear TOP1-DPCs induced by low-dose CPT-based therapy that facilitates the aggregate formation of TOP1. Created with BioRender.com.