@article{129c015e45274dd6b11baed1108ebbd5,
title = "Structural visualization of the p53/RNA polymerase II assembly",
abstract = "The master tumor suppressor p53 activates transcription in response to various cellular stresses in part by facilitating recruitment of the transcription machinery to DNA. Recent studies have documented a direct yet poorly characterized interaction between p53 and RNA polymerase II (Pol II). Therefore, we dissected the human p53/Pol II interaction via single-particle cryo-electron microscopy, structural docking, and biochemical analyses. This study reveals that p53 binds Pol II via the Rpb1 and Rpb2 subunits, bridging the DNA-binding cleft of Pol II proximal to the upstream DNA entry site. In addition, the key DNA-binding surface of p53, frequently disrupted in various cancers, remains exposed within the assembly. Furthermore, the p53/Pol II cocomplex displays a closed conformation as defined by the position of the Pol II clamp domain. Notably, the interaction of p53 and Pol II leads to increased Pol II elongation activity. These findings indicate that p53 may structurally regulate DNA-binding functions of Pol II via the clamp domain, thereby providing insights into p53-regulated Pol II transcription.",
keywords = "Cryo-electron microscopy, P53, RNA polymerase II, Structure, Transcription",
author = "Singh, {Sameer K.} and Zhen Qiao and Lihua Song and Vijay Jani and William Rice and Edward Eng and Coleman, {Robert A.} and Liu, {Wei Li}",
note = "Funding Information: We thank S. Zheng for providing Pol II mAb supernatant, D. King for peptides, and the Tjian laboratory tissue culture facility technicians and all of our laboratory members for helpful advice. We are grateful to M. Keogh, Z. Zhang, and T. Meier for critical comments of the manuscript. We also thank S.M. Shenoy, E. Sylvestre, B. Solly, and A. Contois for high-performance computing cluster technical support. We appreciate assistance from the Analytical Imaging Facility at Albert Einstein College of Medicine, especially F.P. Macaluso, L. Cummins, and G.S. Perumal. We specially thank B. Carragher, C.S. Potter, J. Seitsonen, A. Cheng, C.Wigge, A. Raczkowski, and K. Jordan for helpful suggestions and image acquisition. We thank J. Negron and B. Riley for initial image processing, S. Levy for her early label transfer experiments, and G. Hamilton for programming support. This study was supported by an Albert Einstein College of Medicine start-up fund. Some of this work was performed at the Simons Electron Microscopy Center at the New York Structural Biology Center, which is supported by a grant from the Simons Foundation (grant no. 349247) with additional support from National Institutes of Health (S10 OD019994-01, S10 RR029300-01, S10 RR017291-01, and C06 RR017528-01-CEM), the Agouron Institute (grant no. F00316), and Empire State Development{\textquoteright}s Division of Science, Technology, and Innovation (NYSTAR). W.-L.L. is an affiliated member of the New York Structural Biology Center. Publisher Copyright: {\textcopyright} 2016 Singh et al.",
year = "2016",
month = nov,
day = "15",
doi = "10.1101/gad.285692.116",
language = "English (US)",
volume = "30",
pages = "2527--2537",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "22",
}
