Research Highlights & Biography

Keith Caldecott obtained his BSc (Hons) at Sheffield Unversity (1987) and developed an interest in how cells repair DNA strand breaks during his PhD in the laboratory of Penny Jeggo, at the Medical Research Council’s National Institute for Medical Research (London). Keith's interest in DNA repair continued during postdoctoral fellowships with Larry Thompson (California) and the Nobel Laureate Tomas Lindahl FRS (London), and in 1995 Keith established his own laboratory at the University of Manchester. In 2002 the Caldecott lab moved to the Genome Damage and Stability Centre (GDSC); a multi-disciplinary centre-of-excellence funded jointly by the MRC and the University of Sussex.

Highlights from the Caldecott laboratory include establishing that the dual function DNA kinase/DNA phosphatase enzyme PNKP works in concert with XRCC1 during DNA single-strand break repair (Whitehouse et al, Cell, 2001), that the protein kinase CK2 is a bona fide DNA damage response protein (Loizou et al, Cell, 2004), and that specific hereditary neurodegenerative diseases are associated with cellular defects in chromosomal SSBR (El Khamisy et al, Nature, 2005; Hoch et al Nature 2017). The Caldecott laboratory also identified the first 5’-tyrosyl DNA phosphodiesterase activity (TDP2) in human cells (Cortes-Ledesma et al, Nature 2009), and associated the loss of TDP2 with transcriptional dysfunction and human neurodegenerative disease (Gomes-Herreros et al, Nature Genetics 2014).

More recently, the Caldecott lab has idenitifed a role for base excision repair in epigenetic reprogramming in neurons (Wu et al, Nature 2021), the repair of sunlight-induced photoproducts (Gautam et al, Molecular Cell, 2023), and a role for the central base excision repair scaffold protein (XRCC1) in suppressing endogenous PARP1 hyperactivity and "trapping" (Demin et al Molecular Cell, 2021; Adamowicz et al, Nature Cell Biology, 2021). The Caldecott lab is also currently pursung their discovery that the DNA strand break sensor protein PARP1 senses unligated Okazaki fragments during normal DNA replication, and is characterising the importance of this role for genome stability and cancer therapy (Hanzlikova et al, Molecular Cell, 2018; Vaitsiankova et al, Nat. Struct. Mol. Biol.,  2022).

In 2010 Keith was elected a member of EMBO, in 2012 was elected a member of the Academy of Medical Sciences (FMedSci), and in 2023 was elected a Fellow of the Royal Society (FRS).