The linker histone GH1-HMGA1 is involved in telomere stability and DNA damage repair

First author: Cyril Charbonnel; Affiliations: Université Clermont Auvergne (克莱蒙奥弗涅大学): Clermont-Ferrand, France

Corresponding author: Simon Amiard

Despite intensive searches, few proteins involved in telomere homeostasis (端粒) have been identified in plants. Here, we used pull-down assays (蛋白质体外结合实验) to identify potential telomeric interactors in the model plant species Arabidopsis (Arabidopsis thaliana). We identified the candidate protein GH1-HMGA1 (also known as HON4), an uncharacterised linker histone protein of the high mobility group protein A (HMGA; 高迁移率族蛋白) family in plants. HMGAs are architectural transcription factors (构筑性转录因子) and have been suggested to function in DNA damage repair, but their precise biological roles remain unclear. Here, we show that GH1-HMGA1 is required for efficient DNA damage repair and telomere integrity (端粒完整) in Arabidopsis. GH1-HMGA1 mutants exhibit developmental and growth defects, accompanied by ploidy defects, increased telomere dysfunction-induced foci (端粒功能失调诱导病灶), mitotic anaphase bridges (有丝分裂后期桥) and degraded telomeres. Furthermore, mutants have a higher sensitivity to genotoxic agents (遗传毒物) such as Mitomycin C (丝裂霉素C) and gamma irradiation (伽玛辐照). Our work also suggests that GH1-HMGA1 is directly involved in the repair process by allowing completion of homologous recombination.

在植物中，很少有参与调控端粒稳态的蛋白被确定地鉴定出来。本文利用体外蛋白质结合试验鉴定了模式植物拟南芥中潜在的端粒互作因子。作者鉴定了一个候选蛋白，叫做GH1-HMGA1，该蛋白植物高迁移率族蛋白HMGA家族中未被注释功能的一员。HMGAs属于构筑性转录因子（通过与DNA结合改变染色质的结构，使之发生弯曲、拉伸、卷曲、成环或解链，从而调节靶基因的转录），并被认为在DNA损伤修复过程中发挥作用，然而其精确的生物学功能还不清楚。本文的研究显示GH1-HMGA1对于拟南芥有效的DNA损伤修复和端粒完整性是必需的。GH1-HMGA1突变体因为染色体倍性的缺陷、增加的端粒功能失调诱导病灶、有丝分裂后期桥和端粒降解等原因导致植株存在发育和生长方面的缺陷。此外，突变体对于丝裂霉素C和伽玛辐照的对遗传有害的物质更加敏感。本文的工作揭示了GH1-HMGA1通过保证同源重组的顺利完成从而直接参与到DNA损伤修复过程中。

doi: https://doi.org/10.1104/pp.17.01789

Journal: Plant Physiology

First Published date: 05 April, 2018

（P.S. 欢迎关注微信公众号：微信号Plant_Frontiers）