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DNA Repair

Poor repair of DNA damage is a major cause of cancer. Understanding DNA repair pathways should enable us to prevent early stage cancer from progressing.

Group Head: Dr Chris Jolly

Dr Chris Jolly started his research career as a PhD student in agricultural research in the CSIRO to identify a new gene important for wheat quality. This happened to be part of newly emerging gene family known as defensins, which is also important for wheat defence against microbial attack.

The relationship between plant defensins and human chemokines inspired a move into immunology research. Dr Jolly spent a brief period investigating infection of immune T cells by retroviruses at the Australian National University before obtaining a post-doctoral position at the MRC Laboratory of Molecular Biology in Cambridge UK. This is where his current research interest in physiological mechanisms of gene mutation in immune B cells began.

In Cambridge, Dr Jolly developed techniques that have since been used by researchers around the world to identify a number of molecular pathways involved in B cell gene mutation. Dr Jolly also demonstrated that the majority of protective antibody circulation in adults is derived from B cells which have undergone antibody gene mutation.

Chris and George working in the DNA LabUpon returning to Australia to a position at the Centenary Institute in Sydney in 1998, Dr Jolly established his own research program to investigate the mechanism of antibody gene mutation in B cells, and its relationship to cancer.

Dr Jolly’s group has since demonstrated multiple roles for the DNA repair protein DNA-PKcs in antibody gene mutation. The group currently focuses on the role of the cell replication cycle in gene mutation and have developed unique reagents allowing us to identify exactly when in the cell cycle DNA damage and DNA repair events occur.

About the DNA Repair Group

The DNA Repair Group aims to understand how the many pathways available to cells to carry out DNA repair interact and how they coordinate to deal with different types of gene damage. Additionally, the group hope to identify the steps in antibody hypermutation that are most prone to causing bystander damage of cancer-causing genes.

The group studies molecular pathways that repair damage to DNA and genes. Genes are continuously damaged by irradiation, chemicals and replication errors. Faithful repair of damage is essential to maintain the function of cells and to prevent the accumulation of cancer-causing gene mutations.

Research focus

The DNA Repair Group use the mutation of antibody genes in B cells (white blood cells that secrete antibodies) as a physiologically-relevant model of DNA damage. Antibody gene mutation is a natural process of extremely accelerated gene mutation (i.e. hypermutation) that occurs in lymph nodes during immune responses in order to increase the diversity of antibodies able to neutralise an infectious organism.

Antibody hypermutation is essential for effective immune responses, but occasionally the antibody hypermutation machinery targets the wrong genes (referred to as “bystander” genes) and cause cancer. In fact, mutation of bystander genes by the antibody hypermutation machinery is implicated in the majority of adult B cell lymphomas and leukaemias.

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© 2014 Centenary Institute of Cancer Medicine and Cell Biology.