The role of FACT in managing chromatin: disruption, assembly, or repair?
The role of FACT in managing chromatin: disruption, assembly, or repair?
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DOI：
10.1093/nar/gkaa912
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发表时间：
2020-12-02
影响因子：
14.9
通讯作者：
Winston F
中科院分区：
文献类型：
--
作者：
Formosa T;Winston F
FACT(促进染色质转录)长期以来一直被认为是一种转录延伸因子，其破坏核小体稳定的能力促进了染色质模板上的RNAPII进程。然而，这只是这种组蛋白伴侣的功能之一，因为事实上，它也在DNA复制中发挥作用。虽然在真核生物中广泛保守，对许多生物体的生存至关重要，但对事实的依赖差别很大，一些分化的细胞在没有事实的情况下正常增殖。因此，尚不清楚事实的核心功能是什么，它们在不同的情况下是否有所不同，以及是什么使事实在某些情况下是必要的，而在另一些情况下不是。在这里，我们回顾了最近的进展，并提出了一个统一的事实活动模型。通过与DNA修复的类比，我们认为FACT破坏和组装核小体的能力使其能够监测和恢复核小体的完整性，作为染色质修复系统的一部分，在染色质修复系统中，DNA包装的破坏被感知并恢复到正常状态。因此，对事实的要求取决于细胞中发生的染色质破坏的程度，以及细胞容忍包装缺陷的能力。因此，事实在转录中的作用将只是维持染色质完整性的更广泛系统的一个方面。
FACT (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.
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影响因子：
11.8
作者：
Chen, Chin-Chi;Bowers, Sarion;Lipinszki, Zoltan;Palladino, Jason;Trusiak, Sarah;Bettini, Emily;Rosin, Leah;Przewloka, Marcin R.;Glover, David M.;O'Neill, Rachel J.;Mellone, Barbara G.
通讯作者：
Mellone, Barbara G.
影响因子：
11.4
作者：
Allain, FHT;Yen, YM;Feigon, J
通讯作者：
Feigon, J
影响因子：
64.8
作者：
Brogaard, Kristin;Xi, Liqun;Wang, Ji-Ping;Widom, Jonathan
通讯作者：
Widom, Jonathan
影响因子：
16
作者：
Doris, Stephen M.;Chuang, James;Winston, Fred
通讯作者：
Winston, Fred
影响因子：
11.6
作者：
Antosz, Wojciech;Pfab, Alexander;Grasser, Klaus D.
通讯作者：
Grasser, Klaus D.