@article{5c97af99052d44b1b220a59a4865e759,
title = "Structure of the p53/RNA polymerase II assembly",
abstract = "The tumor suppressor p53 protein activates expression of a vast gene network in response to stress stimuli for cellular integrity. The molecular mechanism underlying how p53 targets RNA polymerase II (Pol II) to regulate transcription remains unclear. To elucidate the p53/Pol II interaction, we have determined a 4.6 {\AA} resolution structure of the human p53/Pol II assembly via single particle cryo-electron microscopy. Our structure reveals that p53{\textquoteright}s DNA binding domain targets the upstream DNA binding site within Pol II. This association introduces conformational changes of the Pol II clamp into a further-closed state. A cavity was identified between p53 and Pol II that could possibly host DNA. The transactivation domain of p53 binds the surface of Pol II{\textquoteright}s jaw that contacts downstream DNA. These findings suggest that p53{\textquoteright}s functional domains directly regulate DNA binding activity of Pol II to mediate transcription, thereby providing insights into p53-regulated gene expression.",
author = "Liou, {Shu Hao} and Singh, {Sameer K.} and Singer, {Robert H.} and Coleman, {Robert A.} and Liu, {Wei Li}",
note = "Funding Information: We thank S. Zheng and R. Tjian for providing Pol II mAb supernatant. We appreciate assistance from the AIF facility at Albert Einstein College of Medicine (Einstein), especially F. P. Macaluso and L. Cummins. We specially thank B. Carragher, P. Clint, E. Eng and W. Rice for helpful suggestions, cryo-EM sample grid screening and initial image acquisition at the New York Structural Biology Center. We are grateful to Z. Yu and C. Hong at HHMI Janelia Research Campus cryo-EM facilities for help in microscope operation and high-throughput data collection. We also thank F. DiMaio, R.Y. Wang and P. Adonine for helpful discussion regarding structural assignment. We appreciate L. Wang at University of California at Davis for permission to access MPS computing cluster for MD simulation. This work was supported by Einstein start-up fund and NIH/NIGMS grant (1R01GM126045-03 to R. A. Coleman). Initial work was performed at the Simons Electron Microscopy Center and National Resource for Automated Molecular Microscopy located at the New York Structural Biology Center, supported by grants from the Simons Foundation (SF349247), NYSTAR, and the NIH National Institute of General Medical Sciences (GM103310) with additional support from Agouron Institute (F00316) and NIH (OD019994) for Krios1 microscope. Molecular graphics and analyses were performed using UCSF Chimera at the University of California, San Francisco supported by NIH P41-GM103311. W. Liu is an affiliated member of the New York Structural Biology Center. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1038/s42003-021-01934-4",
language = "English (US)",
volume = "4",
journal = "Communications Biology",
issn = "2399-3642",
publisher = "Springer Nature",
number = "1",
}