Structure and function of the chromatin remodeler SMARCAD1 with its nucleosome substrate | CU Experts

AbstractThe ATP-dependent chromatin remodeler SMARCAD1 acts on nucleosomes during DNA repair and transcription, but despite its implication in disease, information on its structure and function is scarce. Chromatin remodelers use a variety of ways to engage nucleosomes, and outcomes of the ATP-dependent reactions vary widely. Here we show that SMARCAD1 transfers the entire histone octamer from one DNA segment to another in an ATP-dependent manner but is also capable ofde novonucleosome assembly from histone octamer, due to its ability to bind all histones simultaneously. We describe the cryoEM structure of SMARCAD1 in complex with a nucleosome and show that it engages its substrate unlike any other chromatin remodeler. Our combined data allow us to put forward a testable model for SMARCAD1 mechanism.One-Sentence SummaryThe single subunit chromatin remodeler SMARCAD1 engages nucleosomes in a unique manner and transfers the entire histone octamer.

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