Chromosomal DNA strand breaks are the commonest and most cytotoxic lesions arising in cells. DNA strand breaks result from the attack of DNA by endogenous free radicals and alkylating agents and because of the intrinsic instability of DNA. 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 (see also http://www.sussex.ac.uk/neurodeg/), cancer, and understanding how this knowledge can be exploited in the clinic.
Our work is funded by: