Structure and function of the histone chaperone FACT - Resolving FACTual issues

被引:75
作者
Gurova, Katerina [1 ]
Chang, Han-Wen [2 ]
Valieva, Maria E. [3 ]
Sandlesh, Poorva [1 ]
Studitsky, Vasily M. [2 ]
机构
[1] Roswell Pk Canc Inst, Dept Cell Stress, Elm & Carlton St, Buffalo, NY 14263 USA
[2] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA
[3] Lomonosov Moscow State Univ, Biol Fac, Moscow 119992, Russia
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS | 2018年 / 1861卷 / 09期
基金
俄罗斯科学基金会;
关键词
SSRP1; SPT16; Chromatin; Histone; Cancer; Transcription; FACILITATES CHROMATIN TRANSCRIPTION; MOBILITY-GROUP BOX; RNA-POLYMERASE-II; NUCLEOSOME CORE PARTICLE; CELL-CYCLE PROGRESSION; MIDDLE DOMAIN REVEALS; DNA-REPLICATION; CK2; PHOSPHORYLATES; CRYSTAL-STRUCTURE; MESSENGER-RNA;
D O I
10.1016/j.bbagrm.2018.07.008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:892 / 904
页数:13
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