Transcriptional Regulation at DSBs: Mechanisms and Consequences

被引：48

作者：

Machour, Feras E. ^{[1
]}

Ayoub, Nabieh ^{[1
]}

机构：

[1] Technion Israel Inst Technol, Dept Biol, IL-3200003 Haifa, Israel

来源：

TRENDS IN GENETICS | 2020年 / 36卷 / 12期

基金：

以色列科学基金会;

关键词：

RNA-POLYMERASE-II; DNA-DAMAGE RESPONSE; DOUBLE-STRAND BREAKS; HISTONE DEACETYLASE INHIBITORS; NEGATIVE ELONGATION-FACTOR; CHROMODOMAIN PROTEIN CDYL; HOMOLOGOUS RECOMBINATION; REPRESSES TRANSCRIPTION; GENOMIC INSTABILITY; REPAIR PATHWAYS;

D O I：

10.1016/j.tig.2020.01.001

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Defective double-strand break (DSB) repair leads to genomic instabilities that may augment carcinogenesis. DSBs trigger transient transcriptional silencing in the vicinity of transcriptionally active genes through multilayered processes instigated by Ataxia telangiectasia mutated (ATM), DNA-dependent protein kinase (DNA-PK), and poly-(ADP-ribose) polymerase 1 (PARP1). Novel factors have been identified that ensure DSB-induced silencing via two distinct pathways: direct inhibition of RNA Polymerase II (Pol II) mediated by negative elongation factor (NELF), and histone code editing by CDYL1 and histone deacetylases (HDACs) that catalyze H3K27me3 and erase lysine crotonylation, respectively. Here, we highlight major advances in understanding the mechanisms underlying transcriptional silencing at DSBs, and discuss its functional implications on repair. Furthermore, we discuss consequential links between DSBsilencing factors and carcinogenesis and discuss the potential of exploiting them for targeted cancer therapy.

引用

页码：981 / 997

页数：17

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