Keith W Caldecott

Summary

Affiliation: University of Sussex
Country: UK

Publications

  1. ncbi request reprint DNA single-strand break repair and spinocerebellar ataxia
    Keith W Caldecott
    Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton, BN1 9RQ, United Kingdom
    Cell 112:7-10. 2003
  2. pmc Synergistic decrease of DNA single-strand break repair rates in mouse neural cells lacking both Tdp1 and aprataxin
    Sherif F El-Khamisy
    Genome Damage and Stability Centre, University of Sussex, Brighton, BN1 9RQ, UK
    DNA Repair (Amst) 8:760-6. 2009
  3. pmc APLF promotes the assembly and activity of non-homologous end joining protein complexes
    Gabrielle J Grundy
    Genome Damage and Stability Centre, University of Sussex, Brighton, UK
    EMBO J 32:112-25. 2013
  4. ncbi request reprint Measurement of chromosomal DNA single-strand breaks and replication fork progression rates
    Claire Breslin
    Genome Damage and Stability Center, University of Sussex, Brighton, United Kingdom
    Methods Enzymol 409:410-25. 2006
  5. pmc DNA 3'-phosphatase activity is critical for rapid global rates of single-strand break repair following oxidative stress
    Claire Breslin
    Genome Damage and Stability Centre, University of Sussex, Brighton, United Kingdom
    Mol Cell Biol 29:4653-62. 2009
  6. pmc TDP2 promotes repair of topoisomerase I-mediated DNA damage in the absence of TDP1
    Zhihong Zeng
    School of Life Sciences, Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK
    Nucleic Acids Res 40:8371-80. 2012
  7. pmc TDP2-dependent non-homologous end-joining protects against topoisomerase II-induced DNA breaks and genome instability in cells and in vivo
    Fernando Gómez-Herreros
    Genome Damage and Stability Centre, University of Sussex, Falmer, United Kingdom
    PLoS Genet 9:e1003226. 2013
  8. pmc APLF (C2orf13) is a novel human protein involved in the cellular response to chromosomal DNA strand breaks
    Natasha Iles
    Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, Sussex, United Kingdom
    Mol Cell Biol 27:3793-803. 2007
  9. doi request reprint PARP-3 and APLF function together to accelerate nonhomologous end-joining
    Stuart L Rulten
    Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, UK
    Mol Cell 41:33-45. 2011
  10. pmc Claspin promotes normal replication fork rates in human cells
    Eva Petermann
    Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, United Kingdom
    Mol Biol Cell 19:2373-8. 2008

Collaborators

Detail Information

Publications50

  1. ncbi request reprint DNA single-strand break repair and spinocerebellar ataxia
    Keith W Caldecott
    Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton, BN1 9RQ, United Kingdom
    Cell 112:7-10. 2003
    ..Three papers have recently associated mutations in putative human SSBR genes with hereditary spinocerebellar ataxia. The emerging links between SSBR and neurodegenerative disorders are discussed...
  2. pmc Synergistic decrease of DNA single-strand break repair rates in mouse neural cells lacking both Tdp1 and aprataxin
    Sherif F El-Khamisy
    Genome Damage and Stability Centre, University of Sussex, Brighton, BN1 9RQ, UK
    DNA Repair (Amst) 8:760-6. 2009
    ..These data provide direct evidence for a requirement for aprataxin during chromosomal single-strand break repair in primary neural cells lacking Tdp1...
  3. pmc APLF promotes the assembly and activity of non-homologous end joining protein complexes
    Gabrielle J Grundy
    Genome Damage and Stability Centre, University of Sussex, Brighton, UK
    EMBO J 32:112-25. 2013
    ....
  4. ncbi request reprint Measurement of chromosomal DNA single-strand breaks and replication fork progression rates
    Claire Breslin
    Genome Damage and Stability Center, University of Sussex, Brighton, United Kingdom
    Methods Enzymol 409:410-25. 2006
    ..We also describe an assay we employ to measure the rate of replication fork progression in mammalian/vertebrate cells in the presence or absence of DNA damage...
  5. pmc DNA 3'-phosphatase activity is critical for rapid global rates of single-strand break repair following oxidative stress
    Claire Breslin
    Genome Damage and Stability Centre, University of Sussex, Brighton, United Kingdom
    Mol Cell Biol 29:4653-62. 2009
    ..These data suggest that DNA 3'-phosphatase activity is critical for rapid rates of chromosomal SSB repair following oxidative stress, and that the XRCC1-PNK interaction ensures that this activity is not rate limiting in vivo...
  6. pmc TDP2 promotes repair of topoisomerase I-mediated DNA damage in the absence of TDP1
    Zhihong Zeng
    School of Life Sciences, Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK
    Nucleic Acids Res 40:8371-80. 2012
    ..Together, our data suggest that Tdp1 and Tdp2 fulfil overlapping roles following Top1-induced DNA damage, but not following Top2-induced DNA damage, in vivo...
  7. pmc TDP2-dependent non-homologous end-joining protects against topoisomerase II-induced DNA breaks and genome instability in cells and in vivo
    Fernando Gómez-Herreros
    Genome Damage and Stability Centre, University of Sussex, Falmer, United Kingdom
    PLoS Genet 9:e1003226. 2013
    ....
  8. pmc APLF (C2orf13) is a novel human protein involved in the cellular response to chromosomal DNA strand breaks
    Natasha Iles
    Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, Sussex, United Kingdom
    Mol Cell Biol 27:3793-803. 2007
    ..These data identify APLF as a novel component of the cellular response to DNA strand breaks in human cells...
  9. doi request reprint PARP-3 and APLF function together to accelerate nonhomologous end-joining
    Stuart L Rulten
    Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, UK
    Mol Cell 41:33-45. 2011
    ..These data identify molecular roles for PARP-3 and APLF in chromosomal DNA double-strand break repair reactions...
  10. pmc Claspin promotes normal replication fork rates in human cells
    Eva Petermann
    Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, United Kingdom
    Mol Biol Cell 19:2373-8. 2008
    ..Consistent with this possibility, depletion of Chk1 and Claspin together doubled the percentage of very slow forks, compared with depletion of either protein alone...
  11. pmc Defective DNA ligation during short-patch single-strand break repair in ataxia oculomotor apraxia 1
    John J Reynolds
    Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, United Kingdom
    Mol Cell Biol 29:1354-62. 2009
    ..These data demonstrate that aprataxin participates in chromosomal SSBR in vivo and suggest that short-patch SSBR arrests in AOA1 because of insufficient nonadenylated DNA ligase...
  12. doi request reprint A human 5'-tyrosyl DNA phosphodiesterase that repairs topoisomerase-mediated DNA damage
    Felipe Cortes Ledesma
    Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton, Sussex BN1 9RQ, UK
    Nature 461:674-8. 2009
    ..TTRAP is, to our knowledge, the first human 5'-tyrosyl DNA phosphodiesterase to be identified, and we suggest that this enzyme is denoted tyrosyl DNA phosphodiesterase-2 (TDP2)...
  13. ncbi request reprint The protein kinase CK2 facilitates repair of chromosomal DNA single-strand breaks
    Joanna I Loizou
    Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, United Kingdom
    Cell 117:17-28. 2004
    ..These data identify a direct role for CK2 in the repair of chromosomal DNA strand breaks and in maintaining genetic integrity...
  14. doi request reprint Single-strand break repair and genetic disease
    Keith W Caldecott
    Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, UK
    Nat Rev Genet 9:619-31. 2008
    ..Here, the molecular mechanisms and organization of the DNA-repair pathways that remove SSBs are reviewed and the connection between defects in these pathways and hereditary neurodegenerative disease are discussed...
  15. pmc Poly(ADP-ribose) polymerase 1 accelerates single-strand break repair in concert with poly(ADP-ribose) glycohydrolase
    Anna E O Fisher
    Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, United Kingdom
    Mol Cell Biol 27:5597-605. 2007
    ..Moreover, we identify PARG as a novel and critical component of SSBR that accelerates this process in concert with PARP-1...
  16. doi request reprint Short-patch single-strand break repair in ataxia oculomotor apraxia-1
    John J Reynolds
    Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, UK
    Biochem Soc Trans 37:577-81. 2009
    ..Strikingly, this defect results from insufficient levels of non-adenylated DNA ligase and short-patch single-strand break repair can be restored in AOA1 extracts, independently of aprataxin, by addition of recombinant DNA ligase...
  17. ncbi request reprint Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1
    Sherif F El-Khamisy
    Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK
    Nature 434:108-13. 2005
    ..These data identify a defect in SSBR in a neurodegenerative disease, and implicate this process in the maintenance of genetic integrity in post-mitotic neurons...
  18. pmc Enhanced radiosensitization of human glioma cells by combining inhibition of poly(ADP-ribose) polymerase with inhibition of heat shock protein 90
    Fiona A Dungey
    Genome Damage and Stability Centre, University of Sussex, Falmer BN1 9RQ, United Kingdom
    Mol Cancer Ther 8:2243-54. 2009
    ..17-AAG is therefore a tumor-specific, replication-dependent radiosensitizer that enhances the effects of PARP inhibition. This combination has therapeutic potential in the management of GBM...
  19. pmc TDP2/TTRAP is the major 5'-tyrosyl DNA phosphodiesterase activity in vertebrate cells and is critical for cellular resistance to topoisomerase II-induced DNA damage
    Zhihong Zeng
    Genome Damage and Stability Centre, Science Park Road, University of Sussex, Falmer, Brighton, BN1 9RQ, United Kingdom
    J Biol Chem 286:403-9. 2011
    ..These data identify an important mechanism for resistance to Top2-induced chromosome breakage and raise the possibility that TDP2 is a significant factor in cancer development and treatment...
  20. ncbi request reprint DNA single-strand breaks and neurodegeneration
    Keith W Caldecott
    Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK
    DNA Repair (Amst) 3:875-82. 2004
    ..However, three papers have recently associated hereditary spinocerebellar ataxia with mutations in genes connected with SSBR. The emerging links between SSBR and neurodegeneration are discussed...
  21. ncbi request reprint TDP1 facilitates repair of ionizing radiation-induced DNA single-strand breaks
    Sherif F El-Khamisy
    Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton, UK
    DNA Repair (Amst) 6:1485-95. 2007
    ..These data expand the type of SSBs processed by TDP1 to include those induced by ionizing radiation, and raise the possibility that TDP1 inhibitors may improve radiotherapy...
  22. ncbi request reprint Evidence that the ATR/Chk1 pathway maintains normal replication fork progression during unperturbed S phase
    Eva Petermann
    Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, UK
    Cell Cycle 5:2203-9. 2006
    ..Here we give an overview of how the ATR/Chk1 pathway responds to exogenously blocked replication and then describe evidence for roles of this pathway during replication in an unperturbed S phase...
  23. pmc PARP-1 dependent recruitment of the amyotrophic lateral sclerosis-associated protein FUS/TLS to sites of oxidative DNA damage
    Stuart L Rulten
    Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9RQ, UK and School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG
    Nucleic Acids Res 42:307-14. 2014
    ..Together, these data suggest that FUS is a component of the cellular response to DNA damage, and that defects in this response may contribute to ALS. ..
  24. pmc A requirement for PARP-1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage
    Sherif F El-Khamisy
    Genome Damage and Stability Centre, University of Sussex, Falmer Brighton BN1 9RQ, UK
    Nucleic Acids Res 31:5526-33. 2003
    ..These results support a model in which the rapid activation of PARP-1 at sites of DNA strand breakage facilitates DNA repair by recruiting the molecular scaffold protein, XRCC1...
  25. ncbi request reprint The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4
    Paula M Clements
    Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN19RQ, UK
    DNA Repair (Amst) 3:1493-502. 2004
    ..Aprataxin is therefore physically associated with both the DNA single-strand and double-strand break repair machinery, raising the possibility that AOA1 is a novel DNA damage response-defective disease...
  26. pmc APLF (C2orf13) is a novel component of poly(ADP-ribose) signaling in mammalian cells
    Stuart L Rulten
    Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, United Kingdom
    Mol Cell Biol 28:4620-8. 2008
    ..We conclude that APLF can accumulate at sites of chromosomal damage via zinc finger-mediated binding to poly(ADP-ribose) and is a novel component of poly(ADP-ribose) signaling in mammalian cells...
  27. ncbi request reprint Cell signaling. The BRCT domain: signaling with friends?
    Keith W Caldecott
    Genome Damage and Stability Center, University of Sussex, Brighton BN1 9RR, UK
    Science 302:579-80. 2003
  28. ncbi request reprint TDP1-dependent DNA single-strand break repair and neurodegeneration
    Sherif F El-Khamisy
    Genome Damage and Stability Centre, University of Sussex Falmer, Brighton BN1 9RQ, UK
    Mutagenesis 21:219-24. 2006
    ..Although it is a rare neurodegenerative disease, understanding the molecular basis of SCAN1 will lead to better understanding of the mechanisms that underpin not only neurodegeneration but also cancer...
  29. doi request reprint DNA strand break repair and neurodegeneration
    Stuart L Rulten
    Genome Damage and Stability Centre, Science Park Road, Falmer, Brighton BN1 9RQ, UK
    DNA Repair (Amst) 12:558-67. 2013
    ....
  30. pmc Impact of PNKP mutations associated with microcephaly, seizures and developmental delay on enzyme activity and DNA strand break repair
    John J Reynolds
    Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton, BN1 9RQ, UK
    Nucleic Acids Res 40:6608-19. 2012
    ....
  31. ncbi request reprint XRCC1 and DNA strand break repair
    Keith W Caldecott
    Genome Damage and Stability Centre, University of Sussex, Science Park Road, BN1 9RQ, Falmer Brighton, UK
    DNA Repair (Amst) 2:955-69. 2003
    ..Models for the repair of single-strand breaks during base excision repair and at direct breaks are presented...
  32. pmc Chk1 requirement for high global rates of replication fork progression during normal vertebrate S phase
    Eva Petermann
    Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK
    Mol Cell Biol 26:3319-26. 2006
    ....
  33. ncbi request reprint One ring to bring them all--the role of Ku in mammalian non-homologous end joining
    Gabrielle J Grundy
    Genome Damage and Stability Centre, Science Park Road, Falmer, Brighton BN1 9RQ, UK Electronic address
    DNA Repair (Amst) 17:30-8. 2014
    ..Here we review the structure and functions of Ku and the proteins with which it interacts during non-homologous end joining. ..
  34. ncbi request reprint Mammalian single-strand break repair: mechanisms and links with chromatin
    Keith W Caldecott
    Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, United Kingdom
    DNA Repair (Amst) 6:443-53. 2007
    ..Here, I present an updated model for the repair of SSBs, and speculate on the possible impact of chromatin structure and remodelling on single-strand break repair (SSBR) processes...
  35. ncbi request reprint Polynucleotide kinase: a versatile molecule makes a clean break
    Keith W Caldecott
    Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, United Kingdom
    Structure 10:1151-2. 2002
  36. ncbi request reprint XRCC3 and Rad51 modulate replication fork progression on damaged vertebrate chromosomes
    Judith Henry-Mowatt
    School of Biological Sciences, University of Manchester, Stopford Building, Oxford Road, United Kingdom
    Mol Cell 11:1109-17. 2003
    ..These data demonstrate that the recombination proteins XRCC3 and Rad51 cooperatively modulate the progression of replication forks on damaged vertebrate chromosomes...
  37. pmc Spatial and temporal cellular responses to single-strand breaks in human cells
    Satoshi Okano
    Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, 980 8575 Sendai, Japan
    Mol Cell Biol 23:3974-81. 2003
    ..Our results show the importance of poly(ADP-ribosyl)ation in sequential cellular responses to SSB...
  38. pmc Interference of papillomavirus E6 protein with single-strand break repair by interaction with XRCC1
    Thomas Iftner
    Sektion Experimentelle Virologie, Universitatsklinikum Tuebingen, Elfriede Aulhorn Strasse 6, D 72076 Tuebingen, Germany
    EMBO J 21:4741-8. 2002
    ..These data identify a novel link between small DNA tumour viruses and DNA repair pathways, and suggest a novel explanation for the development of genomic instability in tissue cells persistently infected with papillomaviruses...
  39. pmc 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
    Jun Nakamura
    Department of Environmental Sciences and Engineering, Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC 27599, USA
    Nucleic Acids Res 31:e104. 2003
    ..These results indicate that the analysis of intracellular NAD(P)H level using water-soluble tetrazolium salt can assess an imbalance of SSB repair in living cells in real time...
  40. pmc Central role for the XRCC1 BRCT I domain in mammalian DNA single-strand break repair
    Richard M Taylor
    School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
    Mol Cell Biol 22:2556-63. 2002
    ....
  41. ncbi request reprint Association of XRCC1 and tyrosyl DNA phosphodiesterase (Tdp1) for the repair of topoisomerase I-mediated DNA lesions
    Isabelle Plo
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institute of Health, Building 37, Room 5068, Bethesda, MD, USA
    DNA Repair (Amst) 2:1087-100. 2003
    ..XRCC1 immunoprecipitates contained Tdp1 polypeptide, and both Tdp1 and PNKP activities, indicating a functional connection between the XRCC1 single-strand break repair pathway and the repair of Top1 covalent complexes by Tdp1 and PNKP...
  42. ncbi request reprint Biophysical characterization of human XRCC1 and its binding to damaged and undamaged DNA
    Rajam S Mani
    Department of Experimental Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta T6G 1Z2, Canada
    Biochemistry 43:16505-14. 2004
    ..Our results suggest that hXRCC1 exhibits preferential binding to DNA with single-strand breaks with a gap size of <5 nucleotides...
  43. ncbi request reprint The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates
    Ivan Ahel
    Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK
    Nature 443:713-6. 2006
    ..These data indicate that neurological disorders associated with APTX mutations may be caused by the gradual accumulation of unrepaired DNA strand breaks resulting from abortive DNA ligation events...
  44. ncbi request reprint XRCC1 stimulates polynucleotide kinase by enhancing its damage discrimination and displacement from DNA repair intermediates
    Rajam S Mani
    Department of Experimental Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada
    J Biol Chem 282:28004-13. 2007
    ..First, XRCC1 enhances the capacity of hPNK to discriminate between strand breaks with 5'-OH termini and those with 5'-phosphate termini; and second, XRCC1 stimulates hPNK activity by displacing hPNK from the phosphorylated DNA product...
  45. pmc Chk1 regulates the density of active replication origins during the vertebrate S phase
    Apolinar Maya-Mendoza
    Faculty of Life Sciences, University of Manchester, MIB, Manchester, UK
    EMBO J 26:2719-31. 2007
    ..The same phenotype is induced in wild-type avian cells when Chk1 or ATM/ATR is inhibited. These observations show that Chk1 regulates replication origin activation and contributes to S-phase progression in somatic vertebrate cells...
  46. ncbi request reprint DNA strand break repair and human genetic disease
    Peter J McKinnon
    Department of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Annu Rev Genomics Hum Genet 8:37-55. 2007
    ..Here we provide an overview of the genetic diseases associated with defects in the repair/response to DNA strand breaks...
  47. pmc XRCC1-DNA polymerase beta interaction is required for efficient base excision repair
    Irina I Dianova
    Radiation and Genome Stability Unit, Medical Research Council, Harwell, Oxfordshire OX11 0RD, UK
    Nucleic Acids Res 32:2550-5. 2004
    ..These data suggest an important role for the XRCC1-Pol beta interaction for coordinating the efficiency of the BER process...
  48. ncbi request reprint An Achilles' heel for breast cancer?
    Keith W Caldecott
    Nat Struct Mol Biol 12:387-8. 2005
  49. doi request reprint DNA damage responses and neurological disease. Preface
    Keith W Caldecott
    DNA Repair (Amst) 7:1009. 2008
  50. pmc TDP1 facilitates chromosomal single-strand break repair in neurons and is neuroprotective in vivo
    Sachin Katyal
    Department Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    EMBO J 26:4720-31. 2007
    ..These data indicate that TDP1 is required for neural homeostasis, and reveal a widespread requisite for TDP1 function in response to acutely elevated levels of Top1-associated DNA strand breaks...