The FANCJ helicase unfolds DNA-protein crosslinks to promote their repair
Denitsa Yaneva, Justin L. Sparks, Maximilian Donsbach, Shubo Zhao, Pedro Weickert, Rachel Bezalel-Buch, Julian Stingele, and Johannes C. Walter (2023 Jan 05) The FANCJ helicase unfolds DNA-protein crosslinks to promote their repair. Molecular Cell. https://doi.org/10.1016/j.molcel.2022.12.005
Summary cited from the article:
Endogenous and exogenous agents generate DNA-protein crosslinks (DPCs), whose replication-dependent degradation by the SPRTN protease suppresses aging and liver cancer. SPRTN is activated after the replicative CMG helicase bypasses a DPC and polymerase extends the nascent strand to the adduct. Here, we identify a role for the 5′-to-3′ helicase FANCJ in DPC repair. In addition to supporting CMG bypass, FANCJ is essential for SPRTN activation. FANCJ binds ssDNA downstream of the DPC and uses its ATPase activity to unfold the protein adduct, which exposes the underlying DNA and enables cleavage of the adduct. FANCJ-dependent DPC unfolding is also essential for translesion DNA synthesis past DPCs that cannot be degraded. In summary, our results show that helicase-mediated protein unfolding enables multiple events in DPC repair.