Abstract

Transcription is the first step of gene expression. Maintain high transcription fidelity during transcription elongation is crucial for the normal biological processes for all living things. Dr. Wang revealed the structural basis for nucleotide selection and catalysis in pol II transcription as well as pol II proofreading mechanism.

In the first area, Dr. Wang revealed that, for the first time, the “trigger loop” of transcribing pol II swings beneath a correct nucleoside triphosphate (NTP) in the nucleotide addition site, forming an extensive network of interactions with the NTP base, sugar, phosphates, and additional pol II residues. These interactions play an important role in substrate selection, ensuring the fidelity of transcription as well as facilitating phosphodiester bond formation.  In the second area, Dr. Wang has recently solved the X-ray crystal structure of pol II in the “backtracked” state. Backtracking enhances the fidelity of transcription by enabling proofreading of the nascent transcript. It is frequently caused by encountering a DNA lesion or incorporating a mismatched nucleotide. Dr. Wang’s work provides a structural framework for understanding the very complex but essential transcription proofreading process.