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bioRxiv · 10.1101/2020.06.30.180471

USP11 deubiquitinates monoubiquitinated SPRTN to repair DNA-protein crosslinks

Perry, M.·Kollala, S. S.·Biegert, M.·Su, G.·Kodavati, M.·Mallard, H.·Kreiling, N.·Holbrook, A.·Ghosal, G.
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Abstract

SUMMARYDNA-protein crosslinks (DPCs) are toxic DNA lesions that interfere with DNA metabolic processes such as replication, transcription and recombination. SPRTN is a replication-coupled DNA-dependent metalloprotease that cleaves proteins crosslinked to DNA to promote DPC repair. SPRTN function is tightly regulated by a monoubiquitin switch that controls SPRTN chromatin accessibility during DPC repair. The deubiquitinase regulating SPRTN function in DPC repair is unknown. Here, we identify USP11 as a SPRTN deubiquitinase. USP11 interacts with SPRTN and cleaves monoubiquitinated SPRTN in cells and in vitro. USP11 depletion impairs SPRTN deubiquitination in response to formaldehyde-induced DPCs. Loss of USP11 causes an accumulation of unrepaired DPCs and cellular hypersensitivity to treatment with DPC-inducing agents. Our findings elucidate the function of USP11 in the regulation of SPRTN monoubiquitination and SPRTN-mediated DPC repair.Competing Interest StatementThe authors have declared no competing interest.View Full Text

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Perry, M., Kollala, S. S., Biegert, M., Su, G., Kodavati, M., Mallard, H., Kreiling, N., Holbrook, A., Ghosal, G.. 2020-07-01. USP11 deubiquitinates monoubiquitinated SPRTN to repair DNA-protein crosslinks. https://doi.org/10.1101/2020.06.30.180471

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