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Genome Damage and Stability

We investigate the responses of cells to genome damage and their relationship to diseases, such as cancer, that can arise as a result.

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Our research interests

Genomes are made up of long molecules of DNA and contain the genetic blueprint that tells every part of the body how to work. Our DNA is continually being damaged; in skin cells by sunlight, in intestinal cells by carcinogens in food and all of our cells are even damaged by some degree simply by existing at body temperature.

Luckily, our cells contain sophisticated mechanisms for repairing this damage, thereby protecting our genomes. These protective processes are the focus of our research - we study the different genetic dieseases in which one of these repair systems is faulty. 

These faulty repair systems can result in affected individuals having very high incidences of cancer (more than 1,000 times higher than in the general population). By discovering the nature of the defects, we are able not only to help diagnose and cure these conditions, but also to gain insights into how cancers arise and develop. 

Our research groups focus on different aspects of DNA damage responses and genome instability. Our main interests include:

• Molecular and Cell Biology

  Keith Caldecott, Chris Chan, Helfrid Hochegger, Timothy Humphrey, Penny Jeggo, Alan Lehmann, Mark O'Driscoll and Evi Soutoglou are molecular and cell biologists studying DNA repair processes, cell cycle control and the replication of damaged DNA in human and other vertebrate cells. They have discovered deficiencies in these processes in several human genetic disorders and are attempting to relate the molecular defects to the clinical features of these disorders.

• Yeast Molecular Genetics

  Tony Carr yeast molecular geneticist, who uses the fission yeast Schizosaccharomyces pombe as a model system to understand DNA damage responses in eukaryotic cells. Investigating cell cycle checkpoints that are triggered by DNA damage and the effects of DNA damage on DNA replication. Jon Baxter, Alessandro Bianchi, Timothy Humphrey, Matt Neale and Ulrich Rass use the budding yeast Saccharomyces cerevisiae as a model system to study DNA replication chromatin remodelling, the regulation of double strand break formation in meiosis, DNA replication and the role of telomeres in the regulation of the telomerase enzyme and the preservation of genome stability.

• Biochemical, Cellular and Structural Properties of Multiprotein Systems

  Aidan Doherty, Antony Oliver and Laurence Pearl are structural biologists, studying the assembly, specificity, and regulation of multi-protein complexes involved in the recognition, repair and signalling of DNA damage. They are also involved in the discovery and development of novel small-molecule inhibitors with application as drugs for the treatment of cancer and other diseases. Aidan Doherty is a protein biochemist, studying biochemical, cellular and structural properties of multiprotein systems involved in DNA repair.

• Diagnoses of Genetic Disorders

  A major focus of several research groups in the GDSC (Caldecott, Jeggo, Lehmann, O’Driscoll) is to understand the relationship between the molecular defects and clinical features of a number of genetic disorders whose underlying causes are defects in the response to DNA damage. They have developed cellular tests for these disorders and we use these tests to confirm or exclude tentative clinical diagnoses.

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Our research groups

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Who we work with