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-Structure paper
Title | Mechanism of curaxin-dependent nucleosome unfolding by FACT. |
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Journal, issue, pages | Front Mol Biosci, Vol. 9, Page 1048117, Year 2022 |
Publish date | Nov 22, 2022 |
Authors | Olesya I Volokh / Anastasia L Sivkina / Andrey V Moiseenko / Anna V Popinako / Maria G Karlova / Maria E Valieva / Elena Y Kotova / Mikhail P Kirpichnikov / Timothy Formosa / Vasily M Studitsky / Olga S Sokolova / |
PubMed Abstract | Human FACT (FACT) is a multifunctional histone chaperone involved in transcription, replication and DNA repair. Curaxins are anticancer compounds that induce FACT-dependent nucleosome unfolding and ...Human FACT (FACT) is a multifunctional histone chaperone involved in transcription, replication and DNA repair. Curaxins are anticancer compounds that induce FACT-dependent nucleosome unfolding and trapping of FACT in the chromatin of cancer cells (c-trapping) through an unknown molecular mechanism. Here, we analyzed the effects of curaxin CBL0137 on nucleosome unfolding by FACT using spFRET and electron microscopy. By itself, FACT adopted multiple conformations, including a novel, compact, four-domain state in which the previously unresolved NTD of the SPT16 subunit of FACT was localized, apparently stabilizing a compact configuration. Multiple, primarily open conformations of FACT-nucleosome complexes were observed during curaxin-supported nucleosome unfolding. The obtained models of intermediates suggest "decision points" in the unfolding/folding pathway where FACT can either promote disassembly or assembly of nucleosomes, with the outcome possibly being influenced by additional factors. The data suggest novel mechanisms of nucleosome unfolding by FACT and c-trapping by curaxins. |
External links | Front Mol Biosci / PubMed:36483541 / PubMed Central |
Methods | EM (single particle) |
Resolution | 22.0 - 37.0 Å |
Structure data | EMDB-15278: Human FACT-nucleosome complex in unfolded state EMDB-15279: Human FACT-nucleosome complex in folded state EMDB-15281: Human multifunctional histone chaperone FACT in open state EMDB-15282: Human multifunctional histone chaperone FACT mutant with truncated SPT16-N-terminal domain in closed state EMDB-15283: Human FACT histone chaperone 3D structure in compact state |
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