Structure of the p53/RNA polymerase II assembly

Area of Science:

• Molecular Biology
• Structural Biology
• Genetics

Background:

• The tumor suppressor p53 protein is crucial for cellular integrity, activating gene expression in response to stress.
• The precise mechanism by which p53 interacts with RNA polymerase II (Pol II) to control transcription is not fully understood.

Purpose of the Study:

• To elucidate the molecular mechanism of the p53/Pol II interaction.
• To determine the structure of the human p53/Pol II assembly.

Main Methods:

• Single particle cryo-electron microscopy (cryo-EM) was used to determine the structure.
• High-resolution structural analysis of the p53/Pol II complex.

Main Results:

• The structure revealed p53's DNA binding domain interacts with Pol II's upstream DNA binding site.
• This interaction induces conformational changes in Pol II, leading to a closed clamp state.
• A potential DNA-binding cavity between p53 and Pol II was identified.
• p53's transactivation domain binds to the Pol II jaw region involved in downstream DNA contact.

Conclusions:

• p53 directly regulates Pol II's DNA binding activity through its distinct functional domains.
• These findings provide structural insights into p53-mediated transcriptional regulation.
• The study clarifies a key aspect of p53's role in managing gene expression networks.