Alan Cheung

Sir Henry Dale Fellow

alan.cheung@ucl.ac.uk

Based at Birkbeck

Personal Website

Molecular mechanisms of eukaryotic transcription.

Complex programmes of transcription define every aspect of an organism's identity and growth, and its dysregulation can cause a wide range of diseases, from cancer to diabetes. Our lab is interested in the mechanisms of eukaryotic gene transcription through chromatin. We study RNA polymerase II and chromatin modification complexes, and our aim is to understand how these large macromolecular machines interact and co-operate during transcriptional regulation. Our most recent focus has been on the histone acetyltransferase complexes SAGA and NuA4. These large complexes are required for transcription on chromatin and are related by their common incorporation of Tra1, a large protein that enables their recruitment to promoters (figure below). Tra1 is also a member of the phosphatidylinositol-3-kinase related kinase (PIKK) family of cellular regulators that includes DNA-PKcs, TOR, ATM, ATR and SMG-1.  PIKKs participate in diverse cellular processes including transcription, DNA repair, metabolism and RNA surveillance and we are also interested in the relationship between PIKKs. We utilise a variety of techniques, including crystallography, cryo-electron microscopy, biochemistry, biophysics and genetics.

Selected publications

Cryo-EM structure of the SAGA and NuA4 coactivator subunit Tra1 at 3.7 angstrom resolution.
Díaz-Santín, L.M., Lukoyanova, N., Aciyan, E. and Cheung, A.C.
eLife (2017) 6:e28384
 
A Movie of RNA Polymerase II Transcription
Cheung, A.C., Cramer, P.
Cell (2012) 149 (7):1431-1437
 
Structural basis of RNA polymerase II backtracking, arrest and reactivation
Cheung, A.C., Cramer, P.
Nature (2011) 471 (7337):249–253