期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 13, 页码 -出版社
MDPI
DOI: 10.3390/ijms23137107
关键词
poly(ADP)-ribose polymerase-1; PARP1; nucleosome; transcription; elongation; olaparib
资金
- National Institutes of Health (NIH) [R21CA220151, RO1GM119398, GM113935]
- Canadian Institutes of Health Research [BMA342854]
- Russian Ministry of Science and Higher Education [075-15-20211062]
This study investigated the role of human PARP1 in transcription through nucleosomes and found that PARP1 facilitates transcription and displacement of core histones during transcription through its NAD+-dependent catalytic activity.
Human poly(ADP)-ribose polymerase-1 (PARP1) is a global regulator of various cellular processes, from DNA repair to gene expression. The underlying mechanism of PARP1 action during transcription remains unclear. Herein, we have studied the role of human PARP1 during transcription through nucleosomes by RNA polymerase II (Pol II) in vitro. PARP1 strongly facilitates transcription through mononucleosomes by Pol II and displacement of core histones in the presence of 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 nucleosomal DNA partially uncoiled from the octamer and allowing Pol II progression along nucleosomal DNA. Anti-cancer drug and PARP1 catalytic inhibitor olaparib strongly represses PARP1-dependent transcription. The data suggest that the negative charge on protein(s) poly(ADP)-ribosylated by PARP1 interact with positively charged DNA-binding surfaces of histones transiently exposed during transcription, facilitating transcription through chromatin and transcription-dependent histone displacement/exchange.
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