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bioRxiv · 10.1101/2022.03.23.485504

SUMO4 regulates DNA double-strand break repair independently of conjugation.

Garvin, A. J.·Lanz, A.·Densham, R. R.·Morris, J. R.
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Abstract

The amplitudes of small-modifier protein signalling through ubiquitin and the Small Ubiquitin-like Modifiers, SUMO1-3, are critical to the correct phasing of DNA repair protein accumulation, activity, and clearance, and for the completion of mammalian DNA double-strand break (DSB) repair. However, how SUMO-conjugate signalling in the response is delineated is poorly understood. At the same time, the role of the non-conjugated SUMO protein, SUMO4, has remained enigmatic. Here we reveal that SUMO4 is required to prevent excessive DNA-damage-induced SUMOylation and deleterious over-accumulation of RAP80. Mechanistically we show SUMO4 acts independently of its conjugation and potentiates SENP1 catalytic activity. These data identify SUMO4 as a SUMO deconjugation component and show SUMO4:SENP1 are critical regulators of DNA-damage-induced SUMO signalling. HighlightsO_LIThe roles of the SUMO family members, SUMO1-4, in DSB repair are not redundant. C_LIO_LISUMO4 conjugation is deleterious. C_LIO_LISUMO4 promotes SENP1 catalytic activity. C_LIO_LISUMO4:SENP1 restrict SUMO-signalling and accumulation of the BRCA1-A complex. C_LI

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Garvin, A. J., Lanz, A., Densham, R. R., Morris, J. R.. 2022-03-23. SUMO4 regulates DNA double-strand break repair independently of conjugation.. https://doi.org/10.1101/2022.03.23.485504

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