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Gurova K , Chang HW , Valieva ME , Sandlesh P , Studitsky VM
Structure and function of the histone chaperone FACT - Resolving FACTual issues
Biochim Biophys Acta Gene Regul Mech. 2018 Jul 25
PMID: 30055319    PMCID: PMC6349528    URL: https://www.ncbi.nlm.nih.gov/pubmed/30055319
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FAcilitates Chromatin Transcription (FACT) has been considered essential for transcription through chromatin mostly based on cell-free experiments. However, FACT inactivation in cells does not cause a significant reduction in transcription. Moreover, not all mammalian cells require FACT for viability. Here we synthesize information from different organisms to reveal the core function(s) of FACT and propose a model that reconciles the cell-free and cell-based observations. We describe FACT structure and nucleosomal interactions, and their roles in FACT-dependent transcription, replication and repair. The variable requirements for FACT among different tumor and non-tumor cells suggest that various FACT-dependent processes have significantly different levels of relative importance in different eukaryotic cells. We propose that the stability of chromatin, which might vary among different cell types, dictates these diverse requirements for FACT to support cell viability. Since tumor cells are among the most sensitive to FACT inhibition, this vulnerability could be exploited for cancer treatment.
Gurova, Katerina Chang, Han-Wen Valieva, Maria E Sandlesh, Poorva Studitsky, Vasily M Journal Article Review R01 CA197967/CA/NCI NIH HHS/ P30 CA016056/CA/NCI NIH HHS/ R01 GM119398/GM/NIGMS NIH HHS/ R21 CA220151/CA/NCI NIH HHS/ R21 CA198395/CA/NCI NIH HHS/ Netherlands Biochim Biophys Acta. 2018 Jul 25. pii: S1874-9399(18)30159-7. doi: 10.1016/j.bbagrm.2018.07.008.