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引用次数: 0
摘要
DNA 上同时存在着多种机制,但其中 RNA 聚合酶(RNAP)是最广泛和最活跃的使用者。如此繁忙的基因组环境的平衡有赖于各种机制的存在,这些机制可以将转录的范围和速度限制在功能水平上。在这个意义上,Sen1 是一个核心角色:利用其易位酶活性,这种蛋白质进化出了将 RNAP 从 DNA 模板上移开的特殊功能,从而结束了转录周期。多年来的研究表明,Sen1 在多种情况下都能利用这一机制,在不同情况下终止所有三种真核生物 RNAP。凭借其螺旋酶活性,Sen1 还被认为在解决共转录基因毒性 R 环(可导致复制叉停滞)方面具有突出功能。在这篇综述中,我们概述了过去和最近关于酵母中 Sen1 及其人类同源物 Senataxin(SETX)功能的研究结果。
Sen1: The Varied Virtues of a Multifaceted Helicase.
Several machineries concurrently work on the DNA, but among them RNA Polymerases (RNAPs) are the most widespread and active users. The homeostasis of such a busy genomic environment relies on the existence of mechanisms that allow limiting transcription to a functional level, both in terms of extent and rate. Sen1 is a central player in this sense: using its translocase activity this protein has evolved the specific function of dislodging RNAPs from the DNA template, thus ending the transcription cycle. Over the years, studies have shown that Sen1 uses this same mechanism in a multitude of situations, allowing termination of all three eukaryotic RNAPs in different contexts. In virtue of its helicase activity, Sen1 has also been proposed to have a prominent function in the resolution of co-transcriptional genotoxic R-loops, which can cause the stalling of replication forks. In this review, we provide a synopsis of past and recent findings on the functions of Sen1 in yeast and of its human homologue Senataxin (SETX).
期刊介绍:
Journal of Molecular Biology (JMB) provides high quality, comprehensive and broad coverage in all areas of molecular biology. The journal publishes original scientific research papers that provide mechanistic and functional insights and report a significant advance to the field. The journal encourages the submission of multidisciplinary studies that use complementary experimental and computational approaches to address challenging biological questions.
Research areas include but are not limited to: Biomolecular interactions, signaling networks, systems biology; Cell cycle, cell growth, cell differentiation; Cell death, autophagy; Cell signaling and regulation; Chemical biology; Computational biology, in combination with experimental studies; DNA replication, repair, and recombination; Development, regenerative biology, mechanistic and functional studies of stem cells; Epigenetics, chromatin structure and function; Gene expression; Membrane processes, cell surface proteins and cell-cell interactions; Methodological advances, both experimental and theoretical, including databases; Microbiology, virology, and interactions with the host or environment; Microbiota mechanistic and functional studies; Nuclear organization; Post-translational modifications, proteomics; Processing and function of biologically important macromolecules and complexes; Molecular basis of disease; RNA processing, structure and functions of non-coding RNAs, transcription; Sorting, spatiotemporal organization, trafficking; Structural biology; Synthetic biology; Translation, protein folding, chaperones, protein degradation and quality control.