Poli Jérôme, Gasser Susan M, Papamichos-Chronakis Manolis
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
University of Montpellier and Centre de Recherche en Biologie Cellulaire (CRBM), UMR5237, CNRS, Montpellier 34095, Cedex 5, France.
Philos Trans R Soc Lond B Biol Sci. 2017 Oct 5;372(1731). doi: 10.1098/rstb.2016.0290.
The accessibility of eukaryotic genomes to the action of enzymes involved in transcription, replication and repair is maintained despite the organization of DNA into nucleosomes. This access is often regulated by the action of ATP-dependent nucleosome remodellers. The INO80 class of nucleosome remodellers has unique structural features and it is implicated in a diverse array of functions, including transcriptional regulation, DNA replication and DNA repair. Underlying these diverse functions is the catalytic activity of the main ATPase subunit, which in the context of a multisubunit complex can shift nucleosomes and carry out histone dimer exchange. studies showed that INO80 promotes replication fork progression on a chromatin template, while it was shown to facilitate replication fork restart after stalling and to help evict RNA polymerase II at transcribed genes following the collision of a replication fork with transcription. More recent work in yeast implicates INO80 in the general eviction and degradation of nucleosomes following high doses of oxidative DNA damage. Beyond these replication and repair functions, INO80 was shown to repress inappropriate transcription at promoters in the opposite direction to the coding sequence. Here we discuss the ways in which INO80's diverse functions help maintain genome integrity.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'.
尽管DNA被组织成核小体,但真核生物基因组对于参与转录、复制和修复的酶的作用仍具有可及性。这种可及性通常由ATP依赖的核小体重塑因子调控。INO80类核小体重塑因子具有独特的结构特征,并涉及多种功能,包括转录调控、DNA复制和DNA修复。这些多样功能的基础是主要ATP酶亚基的催化活性,在多亚基复合物的背景下,它可以移动核小体并进行组蛋白二聚体交换。研究表明,INO80促进染色质模板上的复制叉前进,同时还被证明可在复制叉停滞后促进其重新启动,并在复制叉与转录发生碰撞后帮助在转录基因处驱逐RNA聚合酶II。酵母中最近的研究表明,在高剂量氧化DNA损伤后,INO80参与核小体的普遍驱逐和降解。除了这些复制和修复功能外,INO80还被证明可在与编码序列相反的方向上抑制启动子处的不适当转录。在此,我们讨论INO80的多样功能有助于维持基因组完整性的方式。本文是主题为“DNA修复和信号传导中的染色质修饰剂和重塑因子”特刊的一部分。