AI Article Synopsis
- Human FACT is a protein complex that helps with gene transcription by managing histones and nucleosomes.
- Anticancer drugs called curaxins cause FACT to become trapped on cancer cell chromatin, but the details of this process are not fully understood.
- The study revealed that curaxins lead to a redistribution of FACT within the genome and inhibit FACT's role in transcription by tightly binding to nucleosomes, which this research terms "n-trapping."
Article Abstract
Human FACT (facilitates chromatin transcription) is a multifunctional protein complex that has histone chaperone activity and facilitates nucleosome survival and transcription through chromatin. Anticancer drugs curaxins induce FACT trapping on chromatin of cancer cells (c-trapping), but the mechanism of c-trapping is not fully understood. Here, we show that in cancer cells, FACT is highly enriched within the bodies of actively transcribed genes. Curaxin-dependent c-trapping results in redistribution of FACT from the transcribed chromatin regions to other genomic loci. Using a combination of biochemical and biophysical approaches, we have demonstrated that FACT is bound to and unfolds nucleosomes in the presence of curaxins. This tight binding to the nucleosome results in inhibition of FACT-dependent transcription in vitro in the presence of both curaxins and competitor chromatin, suggesting a mechanism of FACT trapping on bulk nucleosomes (n-trapping).
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Source |
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221510 | PMC |
| http://dx.doi.org/10.1126/sciadv.aav2131 | DOI Listing |
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