... understanding life in molecular detail

Dr Qian Wu

DNA repair, DNA damage response, structural biology, pathway choice

 


Our lab is interested in understanding the molecular mechanism of pathways involved in human DNA damage response and repair. We use structural biology as the main tool to determine the architecture of large protein assemblies function at the damaged DNA ends.

Current major projects include:
  • The mechanism of DNA repair pathway choice
  • BRCA1 interaction network
  • The function of BRCT domains in DNA damage and repair

Human cells are under constant threat of damage from external and internal sources. Accumulated DNA damages lead to cell death and genome instability, which can cause cancer, neurodegenerative disease and ageing. How do cells respond and deal with DNA damages is a fundamental biological question, and it is still not fully understood. Maintaining the integrity of genetic information stored in DNA through various damage response and repair signaling pathways are critical for cellular function and cell survival. Proteins involved in these signaling pathways form a dynamic and complex interaction network. It is crucial to identify and understand the structural and functional mechanisms of these proteins not only as individuals, but more importantly as complexes. These form the objectives of our research.

 

We study DNA double-strand breaks (DSBs), which are the most toxic damages in cells. Human cells have two major pathways for repairing DSBs: Homologous Recombination (HR) and Non-Homologous End Joining (NHEJ). We want to study which proteins are involved in making decisions for the pathway choices through 53BP1 and BRCA1 signaling networks and how they manage to do so. We focus on the structural determinations of these complexes using cryo-EM and X-ray crystallography. Together with various biochemical/biophysical methods and cellular studies, we would like to work out the exact mechanisms of pathway choices of DNA repair at a molecular level.

 

We strongly believe that one of the core values of basic biomedical research is translation into tools and treatment to improve human health. Therefore, through our research, we would like to understand how these decisions go wrong in cancer cells compared with normal cells. This will enable us to identify suitable targets to develop small molecule compounds or peptides that modulate the DNA damage response and repair signaling for future drug discovery, medical applications and ultimately killing cancer cells specifically.

Detailed research programme                  Close ▲
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University Academic Fellow

BSc (University of Bristol) 2004-2007
PhD (University of Cambridge) 2007-2012
Postdoc (University of Cambridge) 2012-2018
Group leader (University of Leeds) 2018-present

Astbury 6.108a
School of Molecular and Cellular Biology
0113 34339235
q.n.wu@leeds.ac.uk

http://qianwulab.org

Selected Publications

  1. Wang, J. L.*, Duboc, C.*, Wu, Q.*, Ochi, T., Liang, S., Tsutakawa, S. E., Lees-Miller, S. P., Nadal, M., Tainer, J. A., Blundell, T. L., Strick, T. R. Dissection of DNA double-strand-break repair using novel single-molecule forceps. Nature structural & molecular biology 25 (6), 482-487 (2018)

  2. Wu, Q.*, Paul, A.*, Su, D., Mehmood, S., Foo, T. K., Ochi, T., Bunting, E. L., Xia, B., Robinson C. V., Wang, B., Blundell, T. L. Structure of BRCA1-Abraxas complex reveals phosphorylation-dependent BRCT dimerization at DNA damage sites. Molecular Cell 61, 1-15 (2016)

  3. Wu, Q., Ochi, T., Chirgadze, D. Y. and Blundell, T. L. Non-homologous end-joining partners in a helical dance: structural studies of XLF-XRCC4 interactions. Biochem. Soc. Trans. 39, 1387-1392 (2011)