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植物 γH2AX 焦点对于正确的 DNA DSB 修复反应是必需的,并且与 E2F 因子共定位。

Plant γH2AX foci are required for proper DNA DSB repair responses and colocalize with E2F factors.

机构信息

Institut de Biologie Moléculaire des Plantes, laboratoire propre du CNRS, (UPR 2357) conventionné avec l'Université de Strasbourg 12, rue du Général Zimmer, 67084 Strasbourg Cedex, France.

Laboratorio de Biología Molecular de Plantas Unidad Académica de Biología Experimental Universidad Autónoma de Zacatecas, Av. Revolución S/N Col. Tierra y Libertad CP, 98615 Guadalupe, Zacatecas, México.

出版信息

New Phytol. 2012 Apr;194(2):353-363. doi: 10.1111/j.1469-8137.2012.04062.x. Epub 2012 Feb 16.

DOI:10.1111/j.1469-8137.2012.04062.x
PMID:22339405
Abstract

Cellular responses to DNA double-strand breaks (DSBs) are linked in mammals and yeasts to the phosphorylated histones H2AX (γH2AX) repair foci which are multiproteic nuclear complexes responsible for DSB sensing and signalling. However, neither the components of these foci nor their role are yet known in plants. In this paper, we describe the effects of γH2AX deficiency in Arabidopsis thaliana plants challenged with DSBs in terms of genotoxic sensitivity and E2F-mediated transcriptional responses. We further establish the existence, restrictive to the G1/S transition, of specific DSB-induced foci containing tobacco E2F transcription factors, in both A. thaliana roots and BY-2 tobacco cells. These E2F foci partially colocalize with γH2AX foci while their formation is ataxia telangiectasia mutated (ATM)-dependent, requires the E2F transactivation domain with its retinoblastoma-binding site and is optimal in the presence of functional H2AXs. Overall, our results unveil a new interplay between plant H2AX and E2F transcriptional activators during the DSB response.

摘要

细胞对 DNA 双链断裂 (DSB) 的反应在哺乳动物和酵母中与磷酸化组蛋白 H2AX(γH2AX)修复焦点相关联,这些修复焦点是多蛋白核复合物,负责 DSB 的感应和信号转导。然而,在植物中,这些焦点的组成部分及其作用尚不清楚。在本文中,我们描述了 γH2AX 缺陷对拟南芥植物在 DSB 挑战下的遗传毒性敏感性和 E2F 介导的转录反应的影响。我们进一步证实了特定的 DSB 诱导焦点的存在,这些焦点在拟南芥根和 BY-2 烟草细胞中仅局限于 G1/S 过渡期,并且包含烟草 E2F 转录因子。这些 E2F 焦点与 γH2AX 焦点部分共定位,而它们的形成依赖于共济失调毛细血管扩张突变(ATM),需要 E2F 反式激活域及其视网膜母细胞瘤结合位点,并且在功能正常的 H2AXs 存在下最佳。总体而言,我们的结果揭示了在 DSB 反应过程中植物 H2AX 和 E2F 转录激活因子之间的新相互作用。

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