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Structural insights into the critical DNA damage sensors DNA-PKcs, ATM and ATR.
Progress in Biophysics and Molecular Biology ( IF 3.8 ) Pub Date : 2019-06-27 , DOI: 10.1016/j.pbiomolbio.2019.06.003
Domagoj Baretic 1 , Taiana Maia de Oliveira 2 , Martina Niess 3 , Paul Wan 3 , Hannah Pollard 3 , Christopher M Johnson 1 , Caroline Truman 3 , Eileen McCall 3 , David Fisher 3 , Roger Williams 1 , Christopher Phillips 2
Affiliation  

ATM, ATR and DNA-PKCs are key effectors of DNA Damage response and have been extensively linked to tumourigenesis and survival of cancer cells after radio/chemotherapy. Despite numerous efforts, the structures of these proteins remained elusive until very recently. The resolution revolution in Cryo-EM allowed for molecular details of these proteins to be seen for the first time. Here we provide a comprehensive review of the structures of ATM, ATR and DNA-PKcs and their complexes and expand with observations springing from our own cryo-EM studies. These observations include a novel conformation of ATR and novel dimeric arrangements of DNA-PKcs.



中文翻译:

对关键DNA损伤传感器DNA-PKcs,ATM和ATR的结构见解。

ATM,ATR和DNA-PKC是DNA损伤反应的关键效应器,与放射/化学疗法后肿瘤的发生和癌细胞的存活有着广泛的联系。尽管付出了许多努力,但直到最近,这些蛋白质的结构仍然难以捉摸。Cryo-EM的分辨率革命使人们首次看到了这些蛋白质的分子细节。在这里,我们对ATM,ATR和DNA-PKcs及其复合物的结构进行了全面综述,并扩展了我们自己的冷冻EM研究得出的观察结果。这些观察结果包括ATR的新构象和DNA-PKcs的新二聚体排列。

更新日期:2019-06-27
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