Biography

Keith Caldecott obtained his BSc (Hons) at Sheffield Unversity (1987) and became interested 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 Tomas Lindahl (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, to date, include establishing that the dual function DNA kinase/DNA phosphate 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; Shen et al, Nature Genetics 2010). The Caldecott laboratory also recently identified the first 5’-tyrosyl DNA phosphodiesterase activity in human cells (Cortes-Ledesma et al, Nature 2009), and identified poly (ADP-ribose) polymerase-3 (PARP-3) as a novel component of the repair of DNA double-strand breaks (Rulten et al, Mol Cell, 2011). In 2010 Keith was elected a member of EMBO, and in 2012 was elected a member of the Academy of Medical Sciences (FMedSci).

Role

Deputy Director of the Genome Damage and Stability Centre & Professor of Biochemistry/Director of Research and Knowledge Exchange in the School of Life Sciences

Community and Business

Keith Caldecott was a member of the CR-UK Biological Sciences Committee (2008-2011) and is currently a member of the MRC Molecular and Cellular Medicine Board

The Caldecott lab is focused on identifying and characterising novel human proteins involved in the repair of DNA strand breaks, 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. Please see the Caldecott lab home page for more detail (http://www.sussex.ac.uk/lifesci/caldecottlab/) 

Keith Caldecott currently supervises three postgraduate research students (PhD), teaches on a 3rd year undergraduate module on genome stability and cancer, and is academic tutor to thirteen undergraduate students.

Student Consultation

Keith can be found (typically) in the Genome Damage and Stability Centre (G3.04) between the hours of 9am and 6pm. Keith can be reached at (almost) any time by email (k.w.caldecott@sussex.ac.uk).

Grundy, Gabrielle L, Rulten, Stuart L, Zeng, Zhihong, Arribas-Bosacoma, Raquel, Iles, Natasha, Manley, Katie, Oliver, Antony and Caldecott, Keith W (2013) APLF promotes the assembly and activity of non-homologous end joining protein complexes. The EMBO journal, 32 (1). pp. 112-125. ISSN 1460-2075

Reynolds, John J, Walker, Alexandra K, Gilmore, Edward C, Walsh, Christopher A and Caldecott, Keith W (2012) Impact of PNKP mutations associated with microcephaly, seizures and developmental delay on enzyme activity and DNA strand break repair. Nucleic Acids Research. ISSN 1362-4962

Zeng, Z, Sharma, A, Ju, L, Murai, J, Umans, L, Vermeire, L, Pommier, Y, Takeda, S, Huylebroeck, D, Caldecott, K and El-Khamisy, S (2012) TDP2 promotes repair of topoisomerase I-mediated DNA damage in the absence of TDP1. Nucleic Acids Research, 40 (17). pp. 8371-8380. ISSN 1362-4962

Rulten, Stuart L, Fisher, Anna E O, Robert, Isabelle, Zuma, Maria C, Rouleau, Michele, Ju , Limei, Poirer, Guy, Reina-San-Martin, Bernardo and Caldecott, Keith W (2011) PARP-3 and APLF function together to accelerate nonhomologous end-joining. Molecular Cell, 41 (1). pp. 33-45. ISSN 1097-2765

Shen, Jun, Gilmore, Edward C, Marshall, Christine A, Haddadin, Mary, Reynolds, John J, Eyaid, Wafaa, Bodell, Adria, Barry, Brenda, Gleason, Danielle, Allen, Kathryn, Ganesh, Vijay S, Chang, Bernard S, Grix, Arthur, Hill, R Sean, Topcu, Meral, Caldecott, Keith W, Barkovich, A James and Walsh, Christopher A (2010) Mutations in PNKP cause microcephaly, seizures and defects in DNA repair. Nature Genetics, 42 (3). 245-U38. ISSN 1061-4036

Cortes Ledesma, Felipe, El-Khamisy, Sherif F, Zuma, Maria C, Osborn, Kay and Caldecott, Keith W (2009) A human 5'-tyrosyl DNA phosphodiesterase that repairs topoisomerase-mediated DNA damage. Nature, 461 (7264). pp. 674-678. ISSN 0028-0836

Lee, Youngsoo, Katyal, Sachin, Li, Yang, El-Khamisy, Sherif F, Russell, Helen R, Caldecott, Keith W and McKinnon, Peter J (2009) The genesis of cerebellar interneurons and the prevention of neural DNA damage require XRCC1. Nature Neuroscience, 12 (8). 973-U35. ISSN 1097-6256

Caldecott, Keith (2008) Single-strand break repair and genetic disease. Nature Reviews Genetics, 9 (8). pp. 619-631. ISSN 0028-0836

Katyal, Sachin, El-Khamisy, Sherif F, Russell, Helen R, Liu, Yang, Ju, Limei, Caldecott, Keith W and McKinnon, Peter J (2007) TDP1 facilitates chromosomal single-strand break repair in neurons and is neuroprotective in vivo. EMBO Journal, 26. pp. 4720-4731. ISSN 0261-4189

El-Khamisy, S F and Caldecott, K W (2007) DNA single-strand break repair and spinocerebellar ataxia with axonal neuropathy-1. Neuroscience, 145 (4). pp. 1260-1266. ISSN 0306-4522

Petermann, Eva, Maya-Mendoza, Apolinar, Zachos, George, Gillespie, David A F, Jackson, Dean A and Caldecott, Keith W (2006) Chk1 requirement for high global rates of replication fork progression during normal vertebrate S phase. Molecular and Cellular Biology, 26 (8). pp. 3319-3326. ISSN 0270-7306

Ahel, Ivan, Rass, Ulrich, El-Khamisy, Sherif F, Katyal, Sachin, Clements, Paula M, McKinnon, Peter J, Caldecott, Keith W and West, Stephen C (2006) The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates. Nature, 443. pp. 713-716. ISSN 0028-0836

Breslin, Claire, Clements, Paula M, El-Khamisy, Sherif F, Petermann, Eva, Iles, Natasha and Caldecott, Keith W (2006) Measurement of chromosomal DNA single-strand breaks and replication fork progression rates. Methods in Enzymology, 409. pp. 410-425. ISSN 0076-6879

El-Khamisy, Sherif F, Saifi, Gulam M, Weinfeld, Michael, Johansson, Fredrik, Helleday, Thomas, Lupski, James R and Caldecott, Keith W (2005) Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1. Nature, 434. pp. 108-113. ISSN 0028-0836

Dianova, Irina I, Sleeth, Kate M, Allinson, Sarah L, Parsons, Jason L, Breslin, Claire, Caldecott, Keith W and Dianov, Grigory L (2004) XRCC1-DNA polymerase beta interaction is required for efficient base excision repair. Nucleic Acids Research, 32 (8). pp. 2550-2555. ISSN 0305-1048

Loizou, Joanna I, El-Khamisy, Sherif F, Zlatanou, Anastasia, Moore, David J, Chan, Douglas W, Qin, Jun, Sarno, Stefania, Meggio, Flavio, Pinna, Lorenzo A and Caldecott, Keith W (2004) The protein kinase CK2 facilitates repair of chromosomal DNA single-strand breaks. Cell, 117 (1). pp. 17-28. ISSN 0092-8674

Nakamura, Jun, Asakura, Shoji, Hester, Susan D, de Murcia, Gilbert, Caldecott, Keith W and Swenberg, James A (2003) Quantitation of intracellular NAD(P)H can monitor an imbalance of DNA single strand break repair in base excision repair deficient cells in real time. Nucleic Acids Research, 31 (17). e104-e104. ISSN 0305-1048

Henry-Mowatt, Judith, Jackson, Dean, Masson, Jean-Yves, Johnson, Penny A, Clements, Paula M, Benson, Fiona E, Thompson, Larry H, Takeda, Shunichi, West, Stephen C and Caldecott, Keith W (2003) XRCC3 and Rad51 modulate replication fork progression on damaged vertebrate chromosomes. Molecular Cell, 11 (4). pp. 1109-1117. ISSN 1097-2765

Caldecott, Keith (2001) Mammalian DNA single-strand break repair: an X-ra(y)ted affair. BioEssays, 23 (5). pp. 447-455. ISSN 0265-9247

Whitehouse, Claire J, Taylor, Richard M, Thistlethwaite, Angela, Zhang, Hong, Karimi-Busheri, Feridoun, Lasko, Dana D, Weinfeld, Michael and Caldecott, Keith W (2001) XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell, 104 (1). pp. 107-117. ISSN 0092-8674