FIGURE

Figure 7.

ID

ZDB-FIG-231005-22

Publication

Anticevic et al., 2023 - Tyrosyl-DNA phosphodiesterase 1 (TDP1) and SPRTN protease repair histone 3 and topoisomerase 1 DNA-protein crosslinks in vivo

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Figure 7.

Model of coordinated action of SPRTN and TDP1 in DNA–protein crosslink repair in human cells and zebrafish model. SPRTN is a general DPC protease that cleaves a wide spectrum of crosslinked proteins, whereas TDP1 removes protein residues bound to the 3′ end of the ssDNA break. Under physiological conditions, these two proteins function independently to resolve total DPCs, including specific TOP1-DPCs. Importantly, resolution of endogenous histone-DPCs originating at abasic (AP) sites depends on SPRTN-mediated proteolysis followed by TDP1 phosphodiesterase activity, by which the crosslinked peptide residue is removed from the DNA backbone. In response to the DNA-damaging agent camptothecin, an epistatic relationship between SPRTN and TDP1 is required for the successful removal of histones and TOP1-DPCs as well as other DPCs at the 3′ ends of ssDNA breaks. The model was created with BioRender.com.

Expression Data

Expression Detail

Antibody Labeling

Phenotype Data

Phenotype Detail

Acknowledgments

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