(图片来自百度百科)
2015年10月27日讯 /生物谷BIOON/ --近日,来自哥本哈根大学的研究人员在国际学术期刊Nature上发表了一项最新研究进展,他们发现了组蛋白H1的新功能,这一发现提升了人们对于细胞如何保护和修复DNA损伤的认识。
由于组蛋白的存在,DNA链能够包绕在组蛋白上形成核小体结构,并可以进一步组装为染色质。一个细胞内的DNA链大约有2米长,而细胞通过将其包绕在组蛋白上形成染色质可以将其压缩100,000倍。
通常来讲,细胞内有5种组蛋白,其中四种为核心组蛋白,它们的功能已经得到大量研究,它们除了在染色质组装方面发挥重要作用,还在许多与DNA编码有关的过程中发挥重要功能,其中包括DNA损伤修复。第五种组蛋白H1负责与核小体间的DNA结合,但目前对于组蛋白H1的功能还没有完全了解清楚。
在这项研究中,研究人员利用质谱技术发现组蛋白H1还可以帮助招募损伤修复蛋白。"目前国际上对于组蛋白的研究主要集中在核心组蛋白,而组蛋白H1得到的关注较少,主要是我们一直没有意识到它也会影响DNA损伤修复过程。我们的研究发现了组蛋白H1在这一过程中发挥重要作用,填补了细胞如何保护DNA这一谜题,为这一领域的研究开启了新的大门。"研究人员这样说道。
他们希望这项新发现可以引导科学家们对组蛋白H1投入更多关注,增加人们对于细胞DNA损伤修复过程的认识,同时也可以为DNA损伤引起的疾病治疗提供新的启示。(生物谷Bioon.com)
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Histone H1 couples initiation and amplification of ubiquitin signalling after DNA damage
Tina Thorslund,Anita Ripplinger,Saskia Hoffmann,Thomas Wild,Michael Uckelmann,Bine Villumsen,Takeo Narita,Titia K. Sixma,Chunaram Choudhary,Simon Bekker-Jensen & Niels Mailand
DNA double-strand breaks (DSBs) are highly cytotoxic DNA lesions that trigger non-proteolytic ubiquitylation of adjacent chromatin areas to generate binding sites for DNA repair factors. This depends on the sequential actions of the E3 ubiquitin ligases RNF8 and RNF168 (refs 1, 2, 3, 4, 5, 6), and UBC13 (also known as UBE2N), an E2 ubiquitin-conjugating enzyme that specifically generates K63-linked ubiquitin chains7. Whereas RNF168 is known to catalyse ubiquitylation of H2A-type histones, leading to the recruitment of repair factors such as 53BP1 (refs 8, 9, 10), the critical substrates of RNF8 and K63-linked ubiquitylation remain elusive. Here we elucidate how RNF8 and UBC13 promote recruitment of RNF168 and downstream factors to DSB sites in human cells. We establish that UBC13-dependent K63-linked ubiquitylation at DSB sites is predominantly mediated by RNF8 but not RNF168, and that H1-type linker histones, but not core histones, represent major chromatin-associated targets of this modification. The RNF168 module (UDM1) recognizing RNF8-generated ubiquitylations11 is a high-affinity reader of K63-ubiquitylated H1, mechanistically explaining the essential roles of RNF8 and UBC13 in recruiting RNF168 to DSBs. Consistently, reduced expression or chromatin association of linker histones impair accumulation of K63-linked ubiquitin conjugates and repair factors at DSB-flanking chromatin. These results identify histone H1 as a key target of RNF8-UBC13 in DSB signalling and expand the concept of the histone code12, 13 by showing that posttranslational modifications of linker histones can serve as important marks for recognition by factors involved in genome stability maintenance, and possibly beyond.