Editorial: The repair of DNA–protein crosslinks

Sun, Yilun; Nitiss, John L.; Pommier, ﻿Yves

doi:10.3389/fmolb.2023.1203479

Cited by 2 publications

(1 citation statement)

References 38 publications

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“…Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a highly conserved repair enzyme dedicated to the excision of TOP-1 DPCs [62]. As TOP-1 DPCs form through a phosphotyrosyl linkage between the DNA backbone and the catalytic tyrosyl residue of TOP-1, TDP1 functions by directly targeting and hydrolyzing this phosphotyrosyl bond, resulting in the release of TOP-1 from the DNA backbone [6,58,[63][64][65][66]. Similarly, TDP2 hydrolyzes the phosphotyrosyl bonds between TOP-2 and the DNA backbone [14,59,62,67].…”

Section: Direct Crosslink Removalmentioning

confidence: 99%

Enzymatic Processing of DNA–Protein Crosslinks

Essawy,

Campbell

2024

Genes

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DNA–protein crosslinks (DPCs) represent a unique and complex form of DNA damage formed by covalent attachment of proteins to DNA. DPCs are formed through a variety of mechanisms and can significantly impede essential cellular processes such as transcription and replication. For this reason, anti-cancer drugs that form DPCs have proven effective in cancer therapy. While cells rely on numerous different processes to remove DPCs, the molecular mechanisms responsible for orchestrating these processes remain obscure. Having this insight could potentially be harnessed therapeutically to improve clinical outcomes in the battle against cancer. In this review, we describe the ways cells enzymatically process DPCs. These processing events include direct reversal of the DPC via hydrolysis, nuclease digestion of the DNA backbone to delete the DPC and surrounding DNA, proteolytic processing of the crosslinked protein, as well as covalent modification of the DNA-crosslinked proteins with ubiquitin, SUMO, and Poly(ADP) Ribose (PAR).

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