PARP-1 modulates nucleosome structure in the absence of NAD+статьяТезисы
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Дата последнего поиска статьи во внешних источниках: 16 января 2019 г.
Аннотация:The mechanisms that guarantee access of transcription factors,polymerases and other effectors to genomic DNA, which istightly packed into chromatin remain poorly understood. Humanpoly-ADP-ribose polymerase 1 (PARP1) is a protein sensor ofDNA breaks, transcriptional regulator and an enzyme responsi-ble for poly-ADP-ribosylation of numerous proteins, includinghistones and chromatin-associated proteins. To study the interac-tion of PARP1 with chromatin, we used three mononucleosomaltemplates, each containing two fluorescent labels placed into dif-ferent parts of nucleosomal DNA: either near the entrance/exitof DNA in/from nucleosome or near the nucleosomal dyad. Eachnucleosomal template contained a short DNA fragment extend-ing from the nucleosomes and supporting PARP1 binding.spFRET microscopy analysis of these nucleosomes in solutionrevealed two subpopulations: compact high-FRET nucleosomes(major subpopulation) and low-FRET nucleosomes containingpartially uncoiled DNA (minor subpopulation). Binding ofPARP1 to nucleosomes in the absence of NAD+results in for-mation of a uniform population of complexes that have an inter-mediate FRET efficiency, indicating global structuralreorganization of the entire nucleosomal DNA. Addition ofNAD+results in dissociation of PARP1 from the nucleosomesand the recovery of the nucleosomal structure. The data suggestthat PARP1 can increase accessibility of nucleosomal DNA forexternal probes by reversibly reorganizing nucleosomes. Thisnewly discovered nucleosome structure-modulating activity ofPARP1 is independent of its catalytic function and likely playsan important role in PARP1-dependent DNA repair. This studywas supported by RFBR grant 17-54-33045.