Keith Caldecott; Research Interests
DNA strand breaks are amongst the commonest and most lethal lesions arising in cells. DNA strand breaks result from an intrinsic level of instability of DNA, from attack by endogenous genotoxins, and as 'programmed' intermediates of cellular processes by which genes are expressed and genomes are duplicated. In addition, DNA strand breaks are induced by exposure to environmental genotoxins such as ionising radiation and anticancer drugs. The repair of DNA breaks is critical for genetic integrity and cell survival in mammalian cells and also for normal embryonic development. Moreover, DNA strand break repair is lost or attenuated in a variety of human genetic diseases, resulting in a range of pathologies including developmental and progressive neurological dysfunction, immunodeficiency, and predisposition to cancer. The Caldecott lab is focused on identifying and characterising novel human proteins involved in the repair of DNA breaks, with focus both on single-strand breaks (in which one strand of the DNA double helix is broken) and double-strand breaks (in which both strands of the DNA double helix are broken), and understanding how these important processes are coordinated at the molecular level.
The Caldecott lab is also examining how defects in DNA strand break repair impact on human health, with particular respect to neurological disease, cancer, and understanding how this knowledge can be exploited in the clinic. For example, this work has uncovered new genetic causes of neurodegeneration, such as mutations in the human DNA repair genes PNKP, TDP2, and XRCC1, and has enabled the Caldecott lab to assist clinicians worldwide on request, in the molecular and genetic diagnosis of DNA damage-associated hereditary diseases.
Keith is an elected member of EMBO, the Academy of Medical Sciences (FMedSci), and a Fellow of the Royal Society (FRS). Keith is currently Co-Director of the Genome Damage and Stability Centre. For more information please see,
https://www.sussex.ac.uk/research/explore-our-research/biological-sciences/gene-hunters
http://www.sussex.ac.uk/neurodeg/
Our work is has been funded by:
