The role of FACT in managing chromatin: disruption, assembly, or repair?
The role of FACT in managing chromatin: disruption, assembly, or repair?
AbstractFACT (FAcilitates Chromatin Transcription) has long been considered to be a transcription elongation factor whose ability to destabilize nucleosomes promotes RNAPII progression on chromatin templates. However, this is just one function of this histone chaperone, as FACT also functions in DNA replication. While broadly conserved among eukaryotes and essential for viability in many organisms, dependence on FACT varies widely, with some differentiated cells proliferating normally in its absence. It is therefore unclear what the core functions of FACT are, whether they differ in different circumstances, and what makes FACT essential in some situations but not others. Here, we review recent advances and propose a unifying model for FACT activity. By analogy to DNA repair, we propose that the ability of FACT to both destabilize and assemble nucleosomes allows it to monitor and restore nucleosome integrity as part of a system of chromatin repair, in which disruptions in the packaging of DNA are sensed and returned to their normal state. The requirement for FACT then depends on the level of chromatin disruption occurring in the cell, and the cell's ability to tolerate packaging defects. The role of FACT in transcription would then be just one facet of a broader system for maintaining chromatin integrity.
- HARVARD MEDICAL SCHOOL
- Harvard University United States
- Harvard Medical School United States
- University of Utah United States
- UNIVERSITY OF UTAH
DNA Replication, Models, Molecular, Protein Conformation, alpha-Helical, Binding Sites, DNA Repair, Transcription, Genetic, High Mobility Group Proteins, DNA, Chromatin Assembly and Disassembly, Nucleosomes, DNA-Binding Proteins, Organ Specificity, Humans, Histone Chaperones, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, RNA Polymerase II, Survey and Summary, Transcriptional Elongation Factors, DNA Damage, Protein Binding
DNA Replication, Models, Molecular, Protein Conformation, alpha-Helical, Binding Sites, DNA Repair, Transcription, Genetic, High Mobility Group Proteins, DNA, Chromatin Assembly and Disassembly, Nucleosomes, DNA-Binding Proteins, Organ Specificity, Humans, Histone Chaperones, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, RNA Polymerase II, Survey and Summary, Transcriptional Elongation Factors, DNA Damage, Protein Binding
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