Thomas Helleday

Summary

Affiliation: University of Oxford
Country: UK

Publications

  1. pmc The ERCC1/XPF endonuclease is required for efficient single-strand annealing and gene conversion in mammalian cells
    Ali Z Al-Minawi
    Institute for Cancer Studies, University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK
    Nucleic Acids Res 36:1-9. 2008
  2. pmc Transcription-associated recombination is independent of XRCC2 and mechanistically separate from homology-directed DNA double-strand break repair
    Linda Savolainen
    Department of Genetics, Microbiology and Toxicology, Arrhenius Laboratory, Stockholm University, S 106 91 Stockholm, Sweden
    Nucleic Acids Res 37:405-12. 2009
  3. ncbi request reprint Homologous recombination in cancer development, treatment and development of drug resistance
    Thomas Helleday
    Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford OX3 7DQ, UK
    Carcinogenesis 31:955-60. 2010
  4. ncbi request reprint DNA repair pathways as targets for cancer therapy
    Thomas Helleday
    Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, off Roosevelt Drive, Headington, Oxford, OX3 7DQ, UK
    Nat Rev Cancer 8:193-204. 2008
  5. ncbi request reprint Amplifying tumour-specific replication lesions by DNA repair inhibitors - a new era in targeted cancer therapy
    Thomas Helleday
    Radiation Oncology and Biology, University of Oxford, Oxford OX3 7DQ, UK
    Eur J Cancer 44:921-7. 2008
  6. doi request reprint CK2 phosphorylation of XRCC1 facilitates dissociation from DNA and single-strand break formation during base excision repair
    Cecilia E Ström
    Department of Genetics, Microbiology and Toxicology, Stockholm University, S 106 91 Stockholm, Sweden
    DNA Repair (Amst) 10:961-9. 2011
  7. pmc The ERCC1/XPF endonuclease is required for completion of homologous recombination at DNA replication forks stalled by inter-strand cross-links
    Ali Z Al-Minawi
    The Institute for Cancer Studies, University of Sheffield, Medical School, Sheffield S10 2RX, UK
    Nucleic Acids Res 37:6400-13. 2009
  8. pmc CHK1 activity is required for continuous replication fork elongation but not stabilization of post-replicative gaps after UV irradiation
    Ingegerd Elvers
    Department of Genetics, Microbiology, and Toxicology, Stockholm University, S 10691, Stockholm, Sweden
    Nucleic Acids Res 40:8440-8. 2012
  9. pmc PARP-3 is a mono-ADP-ribosylase that activates PARP-1 in the absence of DNA
    Olga Loseva
    Department of Genetics, Stockholm University, S 10691 Stockholm, Sweden
    J Biol Chem 285:8054-60. 2010
  10. pmc Spontaneous homologous recombination is induced by collapsed replication forks that are caused by endogenous DNA single-strand breaks
    Nasrollah Saleh-Gohari
    Institute for Cancer Studies, University of Sheffield Medical School, UK
    Mol Cell Biol 25:7158-69. 2005

Collaborators

Detail Information

Publications78

  1. pmc The ERCC1/XPF endonuclease is required for efficient single-strand annealing and gene conversion in mammalian cells
    Ali Z Al-Minawi
    Institute for Cancer Studies, University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK
    Nucleic Acids Res 36:1-9. 2008
    ..Furthermore, we find that SSA is not influenced by inhibition of CDK2 (using Roscovitine), ATM (using Caffeine and KU55933), Chk1 (using CEP-3891) or DNA-PK (using NU7026)...
  2. pmc Transcription-associated recombination is independent of XRCC2 and mechanistically separate from homology-directed DNA double-strand break repair
    Linda Savolainen
    Department of Genetics, Microbiology and Toxicology, Arrhenius Laboratory, Stockholm University, S 106 91 Stockholm, Sweden
    Nucleic Acids Res 37:405-12. 2009
    ..In conclusion, we show that TAR depends on BRCA2 but is independent of XRCC2, and that this recombination pathway is separate from that used to repair a two-ended DNA double-strand break...
  3. ncbi request reprint Homologous recombination in cancer development, treatment and development of drug resistance
    Thomas Helleday
    Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford OX3 7DQ, UK
    Carcinogenesis 31:955-60. 2010
    ..Here, I discuss the diversity of HR and how it impacts on cancer with a particular focus on how HR can be exploited in future anticancer strategies...
  4. ncbi request reprint DNA repair pathways as targets for cancer therapy
    Thomas Helleday
    Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, off Roosevelt Drive, Headington, Oxford, OX3 7DQ, UK
    Nat Rev Cancer 8:193-204. 2008
    ....
  5. ncbi request reprint Amplifying tumour-specific replication lesions by DNA repair inhibitors - a new era in targeted cancer therapy
    Thomas Helleday
    Radiation Oncology and Biology, University of Oxford, Oxford OX3 7DQ, UK
    Eur J Cancer 44:921-7. 2008
    ..The aim of these therapies is to produce similar lesions to those produced by DNA damaging anti-cancer drugs. The difference is that the lesions will be cancer-specific and produce milder side-effects in non-cancerous cells...
  6. doi request reprint CK2 phosphorylation of XRCC1 facilitates dissociation from DNA and single-strand break formation during base excision repair
    Cecilia E Ström
    Department of Genetics, Microbiology and Toxicology, Stockholm University, S 106 91 Stockholm, Sweden
    DNA Repair (Amst) 10:961-9. 2011
    ..In conclusion, our results indicate that phosphorylation of XRCC1 by CK2 facilitates the BER incision step, likely by promoting dissociation from DNA...
  7. pmc The ERCC1/XPF endonuclease is required for completion of homologous recombination at DNA replication forks stalled by inter-strand cross-links
    Ali Z Al-Minawi
    The Institute for Cancer Studies, University of Sheffield, Medical School, Sheffield S10 2RX, UK
    Nucleic Acids Res 37:6400-13. 2009
    ..We also find no additional sensitivity to cisplatin by siRNA co-depletion of XRCC3 and ERCC1, showing that the two proteins act on the same pathway to promote survival...
  8. pmc CHK1 activity is required for continuous replication fork elongation but not stabilization of post-replicative gaps after UV irradiation
    Ingegerd Elvers
    Department of Genetics, Microbiology, and Toxicology, Stockholm University, S 10691, Stockholm, Sweden
    Nucleic Acids Res 40:8440-8. 2012
    ..These data suggest that elongation and stabilization of replicative structures at UV-induced DNA damage are distinct mechanisms, and that CHK1 is only involved in replication elongation...
  9. pmc PARP-3 is a mono-ADP-ribosylase that activates PARP-1 in the absence of DNA
    Olga Loseva
    Department of Genetics, Stockholm University, S 10691 Stockholm, Sweden
    J Biol Chem 285:8054-60. 2010
    ..Altogether, these results suggest that the interaction between PARP-1 and PARP-3 is unrelated to DNA single-strand break repair...
  10. pmc Spontaneous homologous recombination is induced by collapsed replication forks that are caused by endogenous DNA single-strand breaks
    Nasrollah Saleh-Gohari
    Institute for Cancer Studies, University of Sheffield Medical School, UK
    Mol Cell Biol 25:7158-69. 2005
    ....
  11. ncbi request reprint A tumour-derived mutant allele of XRCC2 preferentially suppresses homologous recombination at DNA replication forks
    Atul Mohindra
    Institute for Cancer Studies, University of Sheffield, School of Medicine, Sheffield, UK
    Hum Mol Genet 13:203-12. 2004
    ..They further suggest a critical role for XRCC2 in HRR at replication forks, possibly in the loading of RAD51 onto gapped DNA...
  12. pmc PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination
    Helen E Bryant
    The Institute for Cancer Studies, University of Sheffield, Sheffield, UK
    EMBO J 28:2601-15. 2009
    ..Together, our data suggest that PARP1 and PARP2 detect disrupted replication forks and attract Mre11 for end processing that is required for subsequent recombination repair and restart of replication forks...
  13. ncbi request reprint RAD51 is involved in repair of damage associated with DNA replication in mammalian cells
    Cecilia Lundin
    Department of Genetic and Cellular Toxicology, Arrhenius Laboratory, Stockholm University, S 106 91 Stockholm, Sweden
    J Mol Biol 328:521-35. 2003
    ..This suggests that overexpression of RAD51 prevents long-tract HR occurring during DNA replication. We discuss our results in light of recent models suggested for HR at stalled replication forks...
  14. pmc Homologous recombination mediates S-phase-dependent radioresistance in cells deficient in DNA polymerase eta
    Nils H Nicolay
    Cancer Research UK Medical Research Council Gray Institute for Radiation Oncology and Biology, Oncology Department, Old Road Campus Research Building, University of Oxford, Oxford OX3 7DQ, UK
    Carcinogenesis 33:2026-34. 2012
    ..We propose that pol η protein levels in tumours may potentially be used to identify patients who require treatment with chemo-radiotherapy rather than radiotherapy alone for adequate tumour control...
  15. doi request reprint Transcription inhibition by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) causes DNA damage and triggers homologous recombination repair in mammalian cells
    Ivaylo Stoimenov
    Department of Genetics Microbiology and Toxicology, Stockholm University, Stockholm, Sweden
    Mutat Res 706:1-6. 2011
    ..In conclusion, we show that DRB-induced transcription inhibition is associated with the formation of a lesion that triggers RAD51-dependent homologous recombination repair, required for survival under transcriptional stress...
  16. pmc 6-thioguanine selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance
    Natalia Issaeva
    Department of Genetics, Microbiology, and Toxicology, Stockholm University, Stockholm, Sweden
    Cancer Res 70:6268-76. 2010
    ..Altogether, our data show that 6TG efficiently kills BRCA2-defective tumors and suggest that 6TG may be effective in the treatment of advanced tumors that have developed resistance to PARP inhibitors or platinum-based chemotherapy...
  17. ncbi request reprint Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
    Helen E Bryant
    The Institute for Cancer Studies, University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK
    Nature 434:913-7. 2005
    ..The use of an inhibitor of a DNA repair enzyme alone to selectively kill a tumour, in the absence of an exogenous DNA-damaging agent, represents a new concept in cancer treatment...
  18. ncbi request reprint Thymidine selectively enhances growth suppressive effects of camptothecin/irinotecan in MSI+ cells and tumors containing a mutation of MRE11
    Rene Rodriguez
    Institute for Cancer Studies, University of Sheffield, School of Medicine and Biomedical Sciences, Sheffield, United Kingdom
    Clin Cancer Res 14:5476-83. 2008
    ..Here, we attempt to exploit the altered response of mismatch repair (MMR)-deficient colon cancer cells and tumors to camptothecin or irinotecan and thymidine by combining them to improve therapeutic response...
  19. pmc Transcription inhibition by DRB potentiates recombinational repair of UV lesions in mammalian cells
    Ivaylo Stoimenov
    Department of Genetics, Microbiology, and Toxicology, Stockholm University, Stockholm, Sweden
    PLoS ONE 6:e19492. 2011
    ..Thus, increased RAD51 foci formation correlates with increased cell death, suggesting the existence of a futile HR repair of UV-induced DSBs which is linked to transcription inhibition...
  20. ncbi request reprint Methylated DNA causes a physical block to replication forks independently of damage signalling, O(6)-methylguanine or DNA single-strand breaks and results in DNA damage
    Petra Groth
    Department of Genetics, Microbiology and Toxicology, Stockholm University, S 106 91 Stockholm, Sweden
    J Mol Biol 402:70-82. 2010
    ....
  21. ncbi request reprint Poly(ADP-ribose) polymerase (PARP-1) in homologous recombination and as a target for cancer therapy
    Thomas Helleday
    The Institute for Cancer Studies, University of Sheffield, Medical School, Sheffield, UK
    Cell Cycle 4:1176-8. 2005
    ..We discuss the recent discoveries on the use of PARP-1 inhibitors as a targeted cancer therapy for recombination deficient cancers, such as BRCA2 tumors...
  22. ncbi request reprint Poly(ADP-ribose) polymerase is hyperactivated in homologous recombination-defective cells
    Ponnari Gottipati
    Cancer Research UK Medical Research Council, Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, United Kingdom
    Cancer Res 70:5389-98. 2010
    ..Furthermore, the presence of PAR polymers can be used to identify HR-defective cells that are sensitive to PARP inhibitors, which may be potential biomarkers...
  23. ncbi request reprint Human RECQL5 overcomes thymidine-induced replication stress
    Rachel Blundred
    The Institute for Cancer Studies, University of Sheffield, Sheffield, UK
    DNA Repair (Amst) 9:964-75. 2010
    ..In conclusion, we propose that RECQL5 stabilises the replication fork allowing replication to overcome the effects of thymidine and complete the cell cycle...
  24. pmc Methyl methanesulfonate (MMS) produces heat-labile DNA damage but no detectable in vivo DNA double-strand breaks
    Cecilia Lundin
    Department of Genetics, Microbiology and Toxicology, Stockholm University Svante Arrhenius väg 16, S 106 91 Stockholm, Sweden
    Nucleic Acids Res 33:3799-811. 2005
    ..We speculate that the reason for recombination-deficient cells being sensitive to MMS is due to the role of HR in repair of MMS-induced stalled replication forks, rather than for repair of cellular DSBs or heat-labile damage...
  25. ncbi request reprint Caffeine delays replication fork progression and enhances UV-induced homologous recombination in Chinese hamster cell lines
    Fredrik Johansson
    Department of Genetics, Microbiology and Toxicology, Arrhenius Laboratories for the Natural Sciences, Stockholm University, S 106 91 Stockholm, Sweden
    DNA Repair (Amst) 5:1449-58. 2006
    ..The biological consequence of the former pathway is mutations, while the latter results in chromosomal aberrations...
  26. pmc Inhibition of poly (ADP-ribose) polymerase activates ATM which is required for subsequent homologous recombination repair
    Helen E Bryant
    The Institute for Cancer Studies, University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK
    Nucleic Acids Res 34:1685-91. 2006
    ..Altogether, we suggest that ATM is activated by PARP inhibitor-induced collapsed replication forks and may function upstream of HRR in the repair of certain types of double-strand breaks (DSBs)...
  27. pmc Different roles for nonhomologous end joining and homologous recombination following replication arrest in mammalian cells
    Cecilia Lundin
    Department of Genetic and Cellular Toxicology, Stockholm University, S 106 91 Stockholm, Sweden
    Mol Cell Biol 22:5869-78. 2002
    ..Our data suggest that both NHEJ and HR are involved in repair of arrested replication forks that include a DSB, while HR alone is required for the repair of slowed replication forks in the absence of detectable DSBs...
  28. pmc Poly(ADP-ribose) polymerase (PARP-1) has a controlling role in homologous recombination
    Niklas Schultz
    Department of Genetic and Cellular Toxicology, Arrhenius Laboratory, Stockholm University, S 106 91 Stockholm, Sweden
    Nucleic Acids Res 31:4959-64. 2003
    ..Our data suggest that PARP-1 controls DNA damage recognised by HR and that it is not involved in executing HR as such...
  29. pmc UV stalled replication forks restart by re-priming in human fibroblasts
    Ingegerd Elvers
    Department of Genetics, Microbiology and Toxicology, Stockholm University, S 10691 Stockholm, Sweden
    Nucleic Acids Res 39:7049-57. 2011
    ..If left unfilled, the gaps may collapse into DNA double-strand breaks that are repaired by a recombination pathway, similar to the fate of replication forks collapsed after hydroxyurea treatment...
  30. pmc Homologous recombination repairs secondary replication induced DNA double-strand breaks after ionizing radiation
    Petra Groth
    Department of Genetics, Microbiology and Toxicology, Stockholm University, S 106 91 Stockholm, Sweden
    Nucleic Acids Res 40:6585-94. 2012
    ..Altogether, our data indicate that secondary replication-associated DSBs formed following exposure to IR are major substrates for IR-induced HR repair...
  31. ncbi request reprint RPA mediates recombination repair during replication stress and is displaced from DNA by checkpoint signalling in human cells
    Kate M Sleeth
    The Institute for Cancer Studies, University of Sheffield, Sheffield, UK
    J Mol Biol 373:38-47. 2007
    ..Furthermore, our data suggest that replacement of RPA with the RAD51 and RAD52 proteins is affected by checkpoint signalling...
  32. pmc BRCA2-dependent homologous recombination is required for repair of Arsenite-induced replication lesions in mammalian cells
    Songmin Ying
    The Institute for Cancer Studies, University of Sheffield, Sheffield S10 2RX, UK
    Nucleic Acids Res 37:5105-13. 2009
    ..In addition, BRCA2-deficient cells are sensitive to As[III] and we suggest that As[III] could be exploited as a therapy for HR-deficient tumours such as BRCA1 and BRCA2 mutated breast and ovarian cancers...
  33. doi request reprint Homologous recombination mediates cellular resistance and fraction size sensitivity to radiation therapy
    Navita Somaiah
    Gray Institute for Radiation Oncology and Biology, University of Oxford, UK
    Radiother Oncol 108:155-61. 2013
    ..Here, we investigate response to radiotherapy fraction size using CHO cell lines deficient in specific DNA repair pathways in response to radiation induced DNA double strand breaks (DSB)...
  34. pmc Conservative homologous recombination preferentially repairs DNA double-strand breaks in the S phase of the cell cycle in human cells
    Nasrollah Saleh-Gohari
    The Institute for Cancer Studies, University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK
    Nucleic Acids Res 32:3683-8. 2004
    ..This indicates that the same pathway for conservative HR is employed in the repair of DSBs regardless of phase of the cell cycle and that only the frequency is affected...
  35. ncbi request reprint PCNA on the crossroad of cancer
    Ivaylo Stoimenov
    Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden
    Biochem Soc Trans 37:605-13. 2009
    ....
  36. ncbi request reprint Overexpression of cyclin E does not influence homologous recombination in Chinese hamster cells
    Cecilia Lundin
    Department of Genetic and Cellular Toxicology, Stockholm University, Stockholm, Sweden
    Biochem Biophys Res Commun 296:363-7. 2002
    ..Our data suggest that genetic instability caused by overexpression of cyclin E is not mediated by aberrant homologous recombination...
  37. ncbi request reprint Strand invasion involving short tract gene conversion is specifically suppressed in BRCA2-deficient hamster cells
    Nasrollah Saleh-Gohari
    The Institute for Cancer Studies, University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK
    Oncogene 23:9136-41. 2004
    ..These data suggest that BRCA2-defective hamster cells are impaired in short tract gene conversion but maintain proficiency in sister chromatid exchange...
  38. ncbi request reprint ATM is required for the cellular response to thymidine induced replication fork stress
    Emma Bolderson
    Institute for Cancer Studies, School of Medicine, University of Sheffield, UK
    Hum Mol Genet 13:2937-45. 2004
    ..Taken together, our results implicate ATM in the HRR-mediated rescue of replication forks impaired by thymidine treatment...
  39. pmc Chk1 promotes replication fork progression by controlling replication initiation
    Eva Petermann
    Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom
    Proc Natl Acad Sci U S A 107:16090-5. 2010
    ..Our data suggest that increased replication initiation leads to slow replication fork progression and that Chk1 promotes replication fork progression during normal S phase by controlling replication origin activity...
  40. ncbi request reprint Defects in homologous recombination repair in mismatch-repair-deficient tumour cell lines
    Atul Mohindra
    Institute for Cancer Studies, University of Sheffield School of Medicine, Beech Hill Road, UK
    Hum Mol Genet 11:2189-200. 2002
    ..The increased thymidine sensitivity and the loss of an important pathway for the repair of DNA double-strand breaks create new opportunities for therapies directed specifically against this subset of tumours...
  41. doi request reprint Genotoxicity of alcohol is linked to DNA replication-associated damage and homologous recombination repair
    Natalia Kotova
    Department of Genetics, Arrhenius Laboratory, Stockholm University, SE 106 91 Stockholm, Sweden
    Carcinogenesis 34:325-30. 2013
    ..Altogether, our data indicate that alcohol genotoxicity related to AA produces replication lesions on DNA triggering HR repair...
  42. ncbi request reprint p53 protects from replication-associated DNA double-strand breaks in mammalian cells
    Anuradha Kumari
    The Institute for Cancer Studies, University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK
    Oncogene 23:2324-9. 2004
    ..Altogether, we suggest that the effect of p53 on HR and RAD51 levels and foci can be explained by the idea that p53 suppresses formation of recombinogenic lesions...
  43. pmc Poly (ADP-ribose) polymerase (PARP) is not involved in base excision repair but PARP inhibition traps a single-strand intermediate
    Cecilia E Ström
    Department of Genetics, Microbiology and Toxicology, Stockholm University, S 106 91 Stockholm, Sweden
    Nucleic Acids Res 39:3166-75. 2011
    ..Unexpectedly, addition of PARP inhibitor 2 h after DMS treatment still increased SSB levels indicating ongoing repair even at this late time point...
  44. doi request reprint N-acyl taurines are anti-proliferative in prostate cancer cells
    Vicky Chatzakos
    Department of Genetics, Microbiology and Toxicology, Stockholm University, Svante Arrhenius väg 20C, 10691 Stockholm, Sweden
    Lipids 47:355-61. 2012
    ..In summary, our results show that novel biologically active lipids, the N-acyl taurines, result in reduced proliferation in PC-3 cells...
  45. ncbi request reprint Crystal structure of human MTH1 and the 8-oxo-dGMP product complex
    Linda M Svensson
    Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden
    FEBS Lett 585:2617-21. 2011
    ..The binding of the product induces no major structural changes. The structures reveal the mode of nucleotide binding in MTH1 and provide the structural basis for inhibitor design...
  46. ncbi request reprint Targeting homologous recombination repair defects in cancer
    Bastiaan Evers
    Gray Institute for Radiation Oncology and Biology, University of Oxford, UK
    Trends Pharmacol Sci 31:372-80. 2010
    ..Here we describe recent advances in strategies to identify and target HRD tumours, approaches to overcome resistance, and combinatory strategies to optimize treatment outcome...
  47. doi request reprint Transcription-associated recombination in eukaryotes: link between transcription, replication and recombination
    Ponnari Gottipati
    Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, UK
    Mutagenesis 24:203-10. 2009
    ..In this review, we aim to present the available evidence for TAR in both lower and higher eukaryotes and discuss its possible mechanisms, with emphasis on its connection with replication...
  48. pmc Hydroxyurea-stalled replication forks become progressively inactivated and require two different RAD51-mediated pathways for restart and repair
    Eva Petermann
    Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford OX3 7DQ, UK
    Mol Cell 37:492-502. 2010
    ..In conclusion, our data suggest that restart of stalled replication forks and HR repair of collapsed replication forks require two distinct RAD51-mediated pathways...
  49. pmc A small interfering RNA screen of genes involved in DNA repair identifies tumor-specific radiosensitization by POLQ knockdown
    Geoff S Higgins
    Gray Institute for Radiation Oncology and Biology, Oxford University, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom
    Cancer Res 70:2984-93. 2010
    ..These findings raise the possibility that POLQ inhibition might be used clinically to cause tumor-specific radiosensitization...
  50. ncbi request reprint Homologous recombination is involved in repair of chromium-induced DNA damage in mammalian cells
    Helen E Bryant
    The Institute for Cancer Studies, University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK
    Mutat Res 599:116-23. 2006
    ..In addition, we find that ERCC1, XRCC1 and DNA-PKcs defective cells are hypersensitive to Cr[VI], indicating that several repair pathways cooperate in repairing Cr[VI]-induced DNA damage...
  51. ncbi request reprint Screening for genotoxicity using the DRAG assay: investigation of halogenated environmental contaminants
    Fredrik Johansson
    Department of Genetics, Microbiology and Toxicology, Stockholm University, SE 106 91, Sweden
    Mutat Res 563:35-47. 2004
    ..However, the usefulness of the selected cell lines to detect oxidative damage may be limited...
  52. pmc Downregulation of SMG-1 in HPV-positive head and neck squamous cell carcinoma due to promoter hypermethylation correlates with improved survival
    Evgenia Gubanova
    Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden
    Clin Cancer Res 18:1257-67. 2012
    ..No studies have yet been conducted linking defects in SMG-1 expression with cancer. We investigated whether deregulation of SMG-1 could be responsible for defects in the DDR in oropharyngeal HNSCC...
  53. ncbi request reprint Specific targeted gene repair using single-stranded DNA oligonucleotides at an endogenous locus in mammalian cells uses homologous recombination
    Jennifer McLachlan
    The Institute for Cancer Studies, University of Sheffield, Sheffield S10 2RX, UK
    DNA Repair (Amst) 8:1424-33. 2009
    ..However, this mutation was not induced in XRCC3 mutant cells deficient in homologous recombination. Thus, our data suggest ssON-mediated targeted gene repair is more efficient in S-phase and involves homologous recombination...
  54. doi request reprint The XPD subunit of TFIIH is required for transcription-associated but not DNA double-strand break-induced recombination in mammalian cells
    Linda Savolainen
    Department of Genetics, Microbiology and Toxicology, Arrhenius Laboratory, Stockholm University, S 106 91 Stockholm, Sweden
    Mutagenesis 25:623-9. 2010
    ..However, the TAR defect may be associated with a general transcription defect in CSB-deficient cells. In conclusion, we show a novel role for the XPD protein in TAR, linking TAR with TCR...
  55. pmc Overexpression of POLQ confers a poor prognosis in early breast cancer patients
    Geoff S Higgins
    Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, UK
    Oncotarget 1:175-84. 2010
    ..These findings, combined with the limited normal tissue expression of POLQ, make it a very appealing target for possible clinical exploitation...
  56. ncbi request reprint DNA double-strand break repair: from mechanistic understanding to cancer treatment
    Thomas Helleday
    Radiation Oncology and Biology, University of Oxford, Oxford OX3 7LJ, UK
    DNA Repair (Amst) 6:923-35. 2007
    ....
  57. ncbi request reprint Biological relevance of DNA polymerase β and translesion synthesis polymerases to cancer and its treatment
    Nils H Nicolay
    Cancer Research UK Medical Research Council Gray Institute, Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK
    Curr Mol Pharmacol 5:54-67. 2012
    ..The potential clinical role of new DNA polymerase inhibitors is discussed and how they may be combined with conventional cytotoxic agents...
  58. pmc Transcription-associated recombination is dependent on replication in Mammalian cells
    Ponnari Gottipati
    Radiation Oncology and Biology, Radiobiology Research Institute, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom
    Mol Cell Biol 28:154-64. 2008
    ..Furthermore, inhibition of transcription suppresses induction of recombination at stalled replication forks, suggesting that recombination may be involved in bypassing transcription during replication...
  59. ncbi request reprint Reduced apoptotic response to camptothecin in CHO cells deficient in XRCC3
    John M Hinz
    Institute for Cancer Studies, University of Sheffield School of Medicine, Beech Hill Road, Sheffield S10 2RX, UK
    Carcinogenesis 24:249-53. 2003
    ..These results suggest that XRCC3 activity may be necessary for efficient entry into apoptosis in response to DSBs...
  60. ncbi request reprint Mitotic defects in XRCC3 variants T241M and D213N and their relation to cancer susceptibility
    Anna Renglin Lindh
    Departmen tof Genetics, Arrhenius Laboratory, Stockholm University, Stockholm, Sweden
    Hum Mol Genet 15:1217-24. 2006
    ..In contrast, cells carrying the XRCC3 D213N variant are able to eliminate aberrant cells by apoptosis, and consistent with this observation, this variant does not seem to be associated with cancer susceptibility...
  61. doi request reprint The relationship between homologous recombination repair and the sensitivity of human epidermis to the size of daily doses over a 5-week course of breast radiotherapy
    Navita Somaiah
    Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, UK
    Clin Cancer Res 18:5479-88. 2012
    ..Human epidermis was used as a model in which proliferation and DNA repair were correlated over 5 weeks of radiotherapy...
  62. ncbi request reprint XRCC1 phosphorylation by CK2 is required for its stability and efficient DNA repair
    Jason L Parsons
    Gray Institute for Radiation Oncology and Biology, University of Oxford, United Kingdom
    DNA Repair (Amst) 9:835-41. 2010
    ..We therefore propose that CK2 plays an important role in DNA repair by contributing to the stability of XRCC1-Lig III complex...
  63. 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...
  64. doi request reprint The underlying mechanism for the PARP and BRCA synthetic lethality: clearing up the misunderstandings
    Thomas Helleday
    Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford OX3 7DQ, UK
    Mol Oncol 5:387-93. 2011
    ..Experimental evidence supporting these novel models to explain the PARP-BRCA synthetic lethality are discussed...
  65. ncbi request reprint Breast cancer stem-like cells show dominant homologous recombination due to a larger S-G2 fraction
    Osama Al-Assar
    Gray Institute for Radiation Oncology and Biology, University of Oxford, Churchill Hospital, UK
    Cancer Biol Ther 11:1028-35. 2011
    ..Although the changes we saw were specific to MDA-MB231, these results merit further investigation and can be crucial in identifying a mechanism responsible for cancer stem cells treatment resistance in primary tumors...
  66. ncbi request reprint Mre11-dependent degradation of stalled DNA replication forks is prevented by BRCA2 and PARP1
    Songmin Ying
    Gray Institute for Radiation Oncology and Biology, Department of Oncology, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
    Cancer Res 72:2814-21. 2012
    ....
  67. pmc Cohesin phosphorylation and mobility of SMC1 at ionizing radiation-induced DNA double-strand breaks in human cells
    Christina Bauerschmidt
    CRUK MRC Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, off Roosevelt Drive, Headington, Oxford OX3 7DQ, UK
    Exp Cell Res 317:330-7. 2011
    ....
  68. doi request reprint Mutagenesis: mutating a gene while reading it
    Thomas Helleday
    Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, OX3 7DQ, UK
    Curr Biol 20:R57-8. 2010
    ..Is it possible to mutate DNA during transcription? A new study shows that UV-damaged DNA is deaminated during transcription, which is a probable mechanism underlying CC tandem mutations found in the p53 gene in skin cancers...
  69. pmc The histone methyltransferase SET8 is required for S-phase progression
    Stine Jørgensen
    Biotech Research and Innovation Centre and 2Centre for Epigenetics, University of Copenhagen, 2200 Copenhagen N, Denmark
    J Cell Biol 179:1337-45. 2007
    ..Overall, we show that SET8 is essential for genomic stability in mammalian cells and that decreased expression of SET8 results in DNA damage and Chk1-dependent S-phase arrest...
  70. ncbi request reprint Pathways for mitotic homologous recombination in mammalian cells
    Thomas Helleday
    Department of Genetic and Cellular Toxicology, Arrhenius Laboratory, Stockholm University, S 106 91 Stockholm, Sweden
    Mutat Res 532:103-15. 2003
    ..Recombination repair at a stalled replication fork may occur in the absence of a DSB intermediate and may result in either SCE or gene conversion. Finally, substrates and pathways involved in spontaneous HR are discussed...
  71. ncbi request reprint Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
    Jirina Bartkova
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, DK 2100 Copenhagen, Denmark
    Nature 444:633-7. 2006
    ..Thus, senescence in human preneoplastic lesions is a manifestation of oncogene-induced DNA replication stress and, together with apoptosis, provides a barrier to malignant progression...
  72. 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...
  73. pmc Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage
    Randi G Syljuåsen
    Institute of Cancer Biology, Department of Cell Cycle and Cancer, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark
    Mol Cell Biol 25:3553-62. 2005
    ..These results may help explain why Chk1 is an essential kinase and should be taken into account when drugs to inhibit this kinase are considered for use in cancer treatment...
  74. ncbi request reprint The role of RAD51 in etoposide (VP16) resistance in small cell lung cancer
    Lasse Tengbjerg Hansen
    Institute of Molecular Pathology, University of Copenhagen, Copenhagen, Denmark
    Int J Cancer 105:472-9. 2003
    ..Finally, we propose RAD51 as a potential target to improve VP16 efficacy and predict tumor resistance in the treatment of SCLC patients...
  75. ncbi request reprint DNA repair rate and etoposide (VP16) resistance of tumor cell subpopulations derived from a single human small cell lung cancer
    Lasse Tengbjerg Hansen
    Institute of Molecular Pathology, University of Copenhagen, Frederik V s vej 11, 5 sal, DK 2100 Copenhagen, Denmark
    Lung Cancer 40:157-64. 2003
    ....
  76. pmc RAD18 and poly(ADP-ribose) polymerase independently suppress the access of nonhomologous end joining to double-strand breaks and facilitate homologous recombination-mediated repair
    Alihossein Saberi
    CREST Research Project, Radiation Genetics, Faculty of Medicine, Kyoto University, Sakyo ku, Kyoto 606 8501, Japan
    Mol Cell Biol 27:2562-71. 2007
    ..In conclusion, higher-eukaryotic cells separately employ PARP1 and Rad18 to suppress the toxic effects of NHEJ during the HR reaction at stalled replication forks...
  77. ncbi request reprint Up-regulation of the error-prone DNA polymerase {kappa} promotes pleiotropic genetic alterations and tumorigenesis
    Clarisse Bavoux
    Institute of Pharmacology and Structural Biology, Centre National de la Recherche Scientifique, Toulouse, France
    Cancer Res 65:325-30. 2005
    ..These data suggest that altered regulation of DNA metabolism might be related to cancer-associated genetic changes and phenotype...
  78. ncbi request reprint The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair
    Claus Storgaard Sørensen
    Danish Cancer Society, Institute of Cancer Biology, DK 2100 Copenhagen, Denmark
    Nat Cell Biol 7:195-201. 2005
    ..These results highlight a crucial role for the Chk1 signalling pathway in protecting cells against lethal DNA lesions through regulation of HRR...