PARP1-mediated PARylation of SPRTN restrains its DNA-protein crosslink repair activity

PARP1- and HPF1-dependent PARylation of SPRTN restrains its DNA-protein crosslink repair activity, with SPRTN-PARless showing faster, higher accumulation at laser damage.

• Why it matters: SPRTN resolves DNA-protein crosslinks, but the mechanism limiting its engagement on chromatin is unclear, leaving a gap in how repair activity is tuned after recruitment.
• What they did: Mass spectrometry identified seven PARylated residues in SPRTN’s C-terminal region; mutating them (SPRTN-PARless) reduced PARylation, and the Nudix homology domain was required for PARP1 interaction and efficient modification.
• The result: PARylation lowered single-stranded DNA binding and PARG reversed this for cell-derived SPRTN; SPRTN-PARless displayed increased autocleavage and accelerated clearance of camptotheci-induced TOP1 cleavage complexes.

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