Vegetation and climate development of the New Jersey hinterland during the late Middle Miocene (IODP Expedition 313 Site M0027)
Vegetation and climate development of the New Jersey hinterland during the late Middle Miocene (IODP Expedition 313 Site M0027)
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DOI：
10.1016/j.palaeo.2017.07.028
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发表时间：
2017-11
期刊：
影响因子：
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通讯作者：
Sabine Prader;U. Kotthoff;F. McCarthy;G. Schmiedl;T. Donders;D. Greenwood
中科院分区：
文献类型：
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作者：
Sabine Prader;U. Kotthoff;F. McCarthy;G. Schmiedl;T. Donders;D. Greenwood
位点特异性组蛋白泛素化在协调对DNA双链断裂（DSB）的反应中起着核心作用。DSB引发由泛素连接酶RNF 168控制的级联事件，其促进修复因子如53 BP 1和BRCA 1在断裂位点侧翼的染色质上的积累。RNF 168也促进其自身的积累，以及它的副产物RNF 169的积累，但它们如何识别泛素化的染色质尚不清楚。使用甲基-TROSY溶液NMR光谱和分子动力学模拟，我们提出了一个原子分辨率模型的人RNF 169结合到一个泛素化的核小体，并验证它通过电子冷冻显微镜。我们确定RNF 169以一种方式结合泛素化的H2 A-Lys 13/Lys 15，这种方式涉及其典型的泛素结合螺旋和一对富含丝氨酸的基序，这些基序与核小体酸性补丁相互作用。这种三管齐下的相互作用机制与53 BP 1结合泛素化H2 A-Lys 15的机制不同，突出了泛素化核小体位点特异性识别的多样性。http://dx.doi.org/10.7554/eLife.23872.001
Site-specific histone ubiquitylation plays a central role in orchestrating the response to DNA double-strand breaks (DSBs). DSBs elicit a cascade of events controlled by the ubiquitin ligase RNF168, which promotes the accumulation of repair factors such as 53BP1 and BRCA1 on the chromatin flanking the break site. RNF168 also promotes its own accumulation, and that of its paralog RNF169, but how they recognize ubiquitylated chromatin is unknown. Using methyl-TROSY solution NMR spectroscopy and molecular dynamics simulations, we present an atomic resolution model of human RNF169 binding to a ubiquitylated nucleosome, and validate it by electron cryomicroscopy. We establish that RNF169 binds to ubiquitylated H2A-Lys13/Lys15 in a manner that involves its canonical ubiquitin-binding helix and a pair of arginine-rich motifs that interact with the nucleosome acidic patch. This three-pronged interaction mechanism is distinct from that by which 53BP1 binds to ubiquitylated H2A-Lys15 highlighting the diversity in site-specific recognition of ubiquitylated nucleosomes.DOI:http://dx.doi.org/10.7554/eLife.23872.001