Flap endonuclease 1 repairs DNA-protein cross-links via ADP-ribosylation-dependent mechanisms.

ABSTRACT: DNA-protein cross-links (DPCs) are among the most detrimental genomic lesions. They are ubiquitously produced by formaldehyde (FA), and failure to repair FA-induced DPCs blocks chromatin-based processes, leading to neurodegeneration and cancer. The type, structure, and repair of FA-induced DPCs remain largely unknown. Here, we profiled the proteome of FA-induced DPCs and found that flap endonuclease 1 (FEN1) resolves FA-induced DPCs. We revealed that FA also damages DNA bases adjoining the DPCs, leading to DPC-conjugated 5' flap structures via the base excision repair (BER) pathway. We also found that FEN1 repairs enzymatic topoisomerase II (TOP2)-DPCs. Furthermore, we report that both FA-induced and TOP2-DPCs are adenosine diphosphate (ADP) ribosylated by poly(ADP-ribose) polymerase 1 (PA

SUBMITTER: Sun Y 

PROVIDER: S-EPMC11721697 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature