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Genes Dev. 2016 Nov 15;30(22):2527-2537. Epub 2016 Dec 5.

Structural visualization of the p53/RNA polymerase II assembly.

Author information

1
Gruss-Lipper Biophotonics Center, Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
2
New York Structural Biology Center, Manhattan, New York 10027, USA.

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:

RNA polymerase II; cryo-electron microscopy; p53; structure; transcription

PMID:
27920087
PMCID:
PMC5159667
DOI:
10.1101/gad.285692.116
[Indexed for MEDLINE]
Free PMC Article

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