The non homologous end-joining (NHEJ) pathway is one of the major cellular mechanisms for repairing double-strand breaks (DSBs) that can arise in genomic DNA. In common with eukaryotic organisms, most prokaryotic, and some archaeal, species possess a conserved NHEJ apparatus. This DSB repair complex is composed of two conserved core proteins, Ku and DNA ligase D (LigD), that together possess all of the break-recognition, end-processing and ligation activities required to facilitate the complex task of DSB repair in stationary phase of the cell cycle. Much of our recent work has focused on understanding the role of the multi-tasking bacterial NHEJ polymerases in DSB break synapsis and repair.

Although the bacterial NHEJ complex is much more minimal than its eukaryotic counterpart, both pathways share a number of common mechanistic features. The simplicity of this DSB repair complex makes it an ideal model system for us to study the molecular mechanisms that co-ordinate the processing and joining of DSBs by the NHEJ pathway and provides us with a conceptual framework for delineating related end-processing reactions in eukaryotic cells.

Co-workers
Nigel Brissett
Ed Bartlett

Publications
Brissett, N.C., Martin, M.J., Pitcher, R.S.,Green, A.J., Juarez, R., Fox, G.C., Blanco, L. & Doherty, A.J. (2011) Structure of a pre-ternary complex involving a prokaryotic NHEJ polymerase.
Mol. Cell 41, 221-231

Brissett N.C. & Doherty A.J. (2009) Repairing DNA double-strand breaks by the prokaryotic non-homologous end-joining pathway.
Biochem. Soc. Trans. 37, 539-545.

Brissett, N.C., Pitcher, R.S. Picher, A.J., Andrade, P. Juarez, R.,  Green, A.J., Dafforn, T., D. Fox, G.C., Blanco, L. & Doherty, A.J. (2007)  Structure of a polymerase-mediated DNA NHEJ synaptic complex
Science 318, 456-459.

Pitcher, R.S., Brissett, N.C. & Doherty, A.J. (2007) Non Homologous End-Joining in Bacteria:  A Microbial Perspective.
Ann. Rev. Microbiol. 61, 258-282.

Pitcher, R.S., Tonkin, L.M.,  Daley,  J.M., Palmbos,  P.L., Green, A.J.,  Velting, T.L., Brzostek, A.,  Korycka-Machala, M.,Cresawn, S.,  Dziadek, J.,  Hatfull, G.F.,  Wilson,  T.E. &  Doherty, A.J.  (2006) Mycobacteriophage Exploit NHEJ to Facilitate Genome Circularization 
Mol. Cell 23, 743-748.