Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.03.01.530659v1?rss=1

Authors: Anticevic, I., Otten, C., Vinkovic, L., Jukic, L., Popovic, M.

Abstract:
DNA-protein crosslinks (DPCs) are very frequent and damaging DNA lesions that affect all DNA transactions, which in turn can lead to the formation of DSBs, genomic instability and cell death. At the organismal level, impaired DPC repair (DPCR) is associated with cancer, aging, and neurodegenerative phenotypes. Despite the severe consequences of DPCs, the mechanisms of the DPCR pathway at the organism level are still largely unknown. SPRTN is a protease that removes most cellular DPCs during replication, whereas tyrosyl-DNA phosphodiesterase 1 repairs one of the most abundant enzymatic DPCs, topoisomerase 1-DPC (TOP1-DPC). How these two enzymes repair DPCs at the organism level is currently unknown. Using the zebrafish animal model and human cells, we demonstrate that TDP1 and SPRTN repair endogenous, camptothecin- and formaldehyde-induced DPCs, including histone H3- and TOP1-DPCs. We show that resolution of H3-DNA crosslinks depends on upstream proteolysis by SPRTN and subsequent peptide removal by TDP1 in RPE1 cells and zebrafish embryos, whereas SPRTN and TDP1 function in different pathways in the repair of endogenous TOP1-DPCs.

Copy rights belong to original authors. Visit the link for more info

Podcast created by Paper Player, LLC