Of Rings and Rods: Regulating Cohesin Entrapment of DNA to Generate Intra- and Intermolecular Tethers.

Of Rings and Rods: Regulating Cohesin Entrapment of DNA to Generate Intra- and Intermolecular Tethers.
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DOI:
10.1371/journal.pgen.1006337
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发表时间:
2016-10
期刊:
影响因子:
4.5
通讯作者:
Skibbens RV
Skibbens RV
中科院分区:
生物学2区
文献类型:
--
作者:
Skibbens RV

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粘着蛋白在DNA修复、肿瘤发生和严重出生缺陷中的临床相关性继续推动着对粘着蛋白结构、调节和酶学的理解。早期的模型描绘了在单个管腔内捕获两个DNA片段的巨大的粘附素环,这些模型基于相互矛盾的发现而逐渐模糊,但是在无数功能中阐明粘附素结构仍然具有挑战性。由于在很大程度上综合使用了广泛的方法,最近的进展开始投光到深处,以前隐藏的cohesin结构。额外的努力同样提供了新的见解,凝聚酶:具体地说,ATP依赖的转换,促进凝聚结合和释放的DNA的发现。结合起来,这些努力建立了一个新的模型,即粘附素主要作为一个相对扁平的结构存在,它只捕获单个DNA分子,随后的ATP水解,乙酰化和寡聚组装将单个DNA片段拴在一起。
The clinical relevance of cohesin in DNA repair, tumorigenesis, and severe birth defects continues to fuel efforts in understanding cohesin structure, regulation, and enzymology. Early models depicting huge cohesin rings that entrap two DNA segments within a single lumen are fading into obscurity based on contradictory findings, but elucidating cohesin structure amid a myriad of functions remains challenging. Due in large part to integrated uses of a wide range of methodologies, recent advances are beginning to cast light into the depths that previously cloaked cohesin structure. Additional efforts similarly provide new insights into cohesin enzymology: specifically, the discoveries of ATP-dependent transitions that promote cohesin binding and release from DNA. In combination, these efforts posit a new model that cohesin exists primarily as a relatively flattened structure that entraps only a single DNA molecule and that subsequent ATP hydrolysis, acetylation, and oligomeric assembly tether together individual DNA segments.
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