The control of replication fork repair and human disease
Our cellular DNA is constantly being assaulted by reactive metabolites and their by-products. Many of the resulting DNA lesions can be repaired throughout the cell cycle. However certain forms of damage such as DNA interstrand cross-links (ICLs) and DNA protein crosslinks (DPCs) are selectively recognised and repaired during DNA replication. ICLs and DPCs block DNA replication and if unrepaired, or misrepaired, produce devastating health conditions. This is exemplified by the inherited syndrome Fanconi anaemia, where patients suffer from bone marrow failure, developmental defects and ultimately a massively increased risk of leukaemia and solid tumours, often in childhood.

A key effector of the Fanconi anaemia DNA repair pathway is XPF/FANCQ protein. XPF is the active subunit of a dimeric endonuclease (XPF-ERCC1), capable of processing damaged replication fork structures.
Despite the clear link between XPF, replication-coupled DNA repair and human disease, very little is known about the mechanism of the recruitment of XPF to damage-arrested forks, and how XPF interacts with and processes these forks. Here, I will present our recent advances that include a biochemical reconstitution of replication fork repair, and new information on the network or proteins that ensure efficient fork repair.
Date: 8 December 2016, 11:00 (Thursday, 9th week, Michaelmas 2016)
Venue: NDM Building, Headington OX3 7FZ
Venue Details: Basement seminar room, NDM Building (please note: not ORCRB)
Speaker: Dr Peter McHugh (University of Oxford, Weatherall Institute of Molecular Medicine)
Organising department: Ludwig Institute for Cancer Research, Oxford Branch
Organisers: Mary Muers (Oxford Ludwig Institute, NDM Experimental Medicine), Alexandra Ward (University of Oxford, Oxford Ludwig Institute, NDM Experimental Medicine), Christina Woodward (Oxford Ludwig Institute, Nuffield Department of Medicine, University of Oxford)
Organiser contact email address: christina.woodward@ludwig.ox.ac.uk
Host: Prof Xin Lu (Ludwig Cancer Research, Oxford Branch)
Part of: Ludwig Institute Seminar Series
Topics: DNA damage, Oncology
Booking required?: Not required
Audience: Members of the University only
Editor: Christina Woodward