DNA double strand breaks (DSBs) represent a significant lesion to a cell which can lead to cell death or the onset of carcinogenesis. A major mechanism for the repair of DNA DSBs is DNA non-homologous end-joining (NHEJ).  In response to DNA damage, NHEJ helps to maintain genomic stability. Curiously, NHEJ also functions to create genetic diversity during immune development. Projects ongoing in the laboratory include:

• How ATM-dependent damage response signalling influences the process of DNA repair. We have shown that the slow component of DSB repair represents the repair of DSBs within regions of heterochromatin. ATM phosphorylates KAP-1, a heterochromatic building protein, and causes relaxation of the heterochromatic superstructure. This allows repair of DSBs within or in the proximity of heterochromatin to occur.
• How Artemis functions in HC-DSB repair. 
• How cell cycle phase influences DSB repair - we know that in G1 phase, DSB repair occurs predominantly by NHEJ but in G2 phase both homologous recombination and NHEJ function
• Identification of defects in NHEJ components in human patients
• The developmental role of NHEJ proteins including the analysis of DSB rejoining in vivo

Collaborators:

Dr. Markus Lobrich, Darmstadt Univeristy of Technology - our wonderful collaborator for many years.

Dr. Susan Lees-Miller, Calgary University.

Dr. Kathy Meek, Michigan State University.