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.
authors.affiliation: Gruss-Lipper Biophotonics Center, Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Sameer K
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Gruss-Lipper Biophotonics Center, Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Qiao
authors.affiliation: Gruss-Lipper Biophotonics Center, Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Lihua
authors.initials: L
authors.lastname: Song
authors.affiliation: Gruss-Lipper Biophotonics Center, Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Vijay
authors.initials: V
authors.lastname: Jani
authors.affiliation: New York Structural Biology Center, Manhattan, New York 10027, USA.
authors.forename: William
authors.initials: W
authors.lastname: Rice
authors.affiliation: New York Structural Biology Center, Manhattan, New York 10027, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Eng
authors.affiliation: Gruss-Lipper Biophotonics Center, Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Coleman
authors.affiliation: Gruss-Lipper Biophotonics Center, Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Liu
mesh_terms: D020285:Cryoelectron Microscopy; D005090:Exodeoxyribonucleases / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D000072417:Protein Domains; D020836:Protein Structure, Quaternary; D012319:RNA Polymerase II / Q000737:chemistry* / Q000378:metabolism*; D061805:Transcription Elongation, Genetic; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D012319:RNA Polymerase II; D005090:Exodeoxyribonucleases; C020133:exodeoxyribonuclease III
keywords: RNA polymerase II; cryo-electron microscopy; p53; structure; transcription