Human PARP1 Facilitates Transcription through a Nucleosome and Histone Displacement by Pol II In Vitroстатья
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Дата последнего поиска статьи во внешних источниках: 13 июля 2022 г.
Аннотация:Human poly(ADP)-ribose polymerase-1 (PARP1) is a global regulator of various cellularprocesses, from DNA repair to gene expression. The underlying mechanism of PARP1 actionduring transcription remains unclear. Herein, we have studied the role of human PARP1 duringtranscription through nucleosomes by RNA polymerase II (Pol II) in vitro. PARP1 strongly facilitatestranscription through mononucleosomes by Pol II and displacement of core histones in the presenceof NAD+ during transcription, and its NAD+-dependent catalytic activity is essential for this process.Kinetic analysis suggests that PARP1 facilitates formation of “open” complexes containing nucleosomalDNA partially uncoiled from the octamer and allowing Pol II progression along nucleosomalDNA. Anti-cancer drug and PARP1 catalytic inhibitor olaparib strongly represses PARP1-dependenttranscription. The data suggest that the negative charge on protein(s) poly(ADP)-ribosylated byPARP1 interact with positively charged DNA-binding surfaces of histones transiently exposed duringtranscription, facilitating transcription through chromatin and transcription-dependent histonedisplacement/exchange.