Research Topics
Genomes and Genes
| Stephen C WestSummaryAffiliation: Cancer Research UK Country: UK Publications
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Detail Information
Publications
Cross-links between Fanconi anaemia and BRCA2Stephen C West
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
DNA Repair (Amst) 2:231-4. 2003..Their results suggest that the six cloned FA genes are linked with BRCA2 in a common pathway. Here Steve West discusses some of the implications of these findings...- Molecular views of recombination proteins and their controlStephen C West
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
Nat Rev Mol Cell Biol 4:435-45. 2003..Many of the enzymes that are involved in recombination have been isolated, and the details of this pathway are now being unravelled at the molecular level... - The search for a human Holliday junction resolvaseStephen C West
London Research Institute, Clare Hall Laboratories, Cancer Research UK, South Mimms, Hertfordshire, UK
Biochem Soc Trans 37:519-26. 2009..GEN1 fits the paradigm developed from studies of prokaryotic Holliday junction resolvases, in that it specifically recognizes junctions and resolves them using a mechanism similar to that exhibited by the Escherichia coli RuvC protein... - FANCM and FAAP24 function in ATR-mediated checkpoint signaling independently of the Fanconi anemia core complexSpencer J Collis
DNA Damage Response Laboratory, Cancer Research UK, Clare Hall, EN6 3LD South Mimms, UK
Mol Cell 32:313-24. 2008..Our data suggest that DNA damage recognition and remodeling activities of FANCM and FAAP24 cooperate with ATR/Chk1 to promote efficient activation of DNA damage checkpoints... - FANCM connects the genome instability disorders Bloom's Syndrome and Fanconi AnemiaAndrew J Deans
London Research Institute, Cancer Research UK, South Mimms, UK
Mol Cell 36:943-53. 2009..Moreover, a common phenotype of BS and FA cells-an elevated frequency of sister chromatid exchanges-was due to a loss of interaction of the two complexes through FANCM... - The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNATina Thorslund
London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Hertfordshire, UK
Nat Struct Mol Biol 17:1263-5. 2010..These observations provide a molecular basis for the role of BRCA2 in the maintenance of genome stability... - Mechanism of Holliday junction resolution by the human GEN1 proteinUlrich Rass
London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts, United Kingdom
Genes Dev 24:1559-69. 2010..However, the unique feature of GEN1 that distinguishes it from other Rad2/XPG nucleases is its ability to dimerize on HJs. This functional adaptation provides the two symmetrically aligned active sites required for HJ resolution... - Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1Dragana Ahel
DNA Damage Response Laboratory, Clare Hall, London Research Institute, South Mimms EN6 3LD, UK
Science 325:1240-3. 2009..Furthermore, we show that depletion or overexpression of ALC1 results in sensitivity to DNA-damaging agents. Collectively, these results provide new insights into the mechanisms by which poly(ADP-ribose) regulates DNA repair... - RAD51 localization and activation following DNA damageMadalena Tarsounas
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK
Philos Trans R Soc Lond B Biol Sci 359:87-93. 2004..Taken together, these observations indicate that BRCA2 plays a critical role in controlling the actions of RAD51 at both the microscopic (focus formation) and molecular (DNA binding) level... - Functional overlap between the structure-specific nucleases Yen1 and Mus81-Mms4 for DNA-damage repair in S. cerevisiaeMiguel G Blanco
London Research Institute, Cancer Research UK, South Mimms, Herts, UK
DNA Repair (Amst) 9:394-402. 2010..These findings indicate that Yen1 can act upon recombination/repair intermediates that arise in MUS81-defective cells following replication fork damage... - RTEL-1 enforces meiotic crossover interference and homeostasisJillian L Youds
DNA Damage Response Laboratory, London Research Institute, Cancer Research UK, Clare Hall, South Mimms, EN6 3LD, UK
Science 327:1254-8. 2010..Two distinct classes of meiotic COs are increased in rtel-1 mutants, and COI and homeostasis are compromised. We propose that RTEL-1 implements the second level of CO control by promoting noncrossovers... - Role of RAD51C and XRCC3 in genetic recombination and DNA repairYilun Liu
Clare Hall Laboratories, London Research Institute, Cancer Research UK, South Mimms, Hertfordshire EN6 3LD, United Kingdom
J Biol Chem 282:1973-9. 2007.... - CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repairFumiko Esashi
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
Nature 434:598-604. 2005.... - Molecular mechanism of DNA deadenylation by the neurological disease protein aprataxinUlrich Rass
London Research Institute, Clare Hall Laboratories, Cancer Research UK, South Mimms, Herts EN6 3LD, United Kingdom
J Biol Chem 283:33994-4001. 2008..These results pinpoint APTX as the first protein to adopt canonical histidine triad-type reaction chemistry for the repair of DNA... - Structural and functional relationships of the XPF/MUS81 family of proteinsAlberto Ciccia
London Research Institute, Cancer Research UK, Clare Hall Laboratories, Hertfordshire, United Kingdom
Annu Rev Biochem 77:259-87. 2008..Determining how these enzymes recognize specific DNA substrates and promote key repair reactions is an important challenge for the future... - Identification of Holliday junction resolvases from humans and yeastStephen C Y Ip
Genetic Recombination Laboratory, Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK
Nature 456:357-61. 2008..Recombinant GEN1 and Yen1 resolve Holliday junctions by the introduction of symmetrically related cuts across the junction point, to produce nicked duplex products in which the nicks can be readily ligated... - Defective DNA repair and neurodegenerative diseaseUlrich Rass
London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK
Cell 130:991-1004. 2007..A picture is emerging to suggest that brain cells, due to their nonproliferative nature, may be particularly prone to the progressive accumulation of unrepaired DNA lesions... - Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCMAlberto Ciccia
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts, UK
Mol Cell 25:331-43. 2007..Our data indicate that the FANCM/FAAP24 complex may play a key role in recruitment of the FA core complex to damaged DNA... - Actions of aprataxin in multiple DNA repair pathwaysUlrich Rass
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK
J Biol Chem 282:9469-74. 2007..We suggest that Aprataxin may have a general proofreading function in DNA repair, removing DNA adenylates as they arise during single-strand break repair, double-strand break repair, and in base excision repair... - Aberrant chromosome morphology in human cells defective for Holliday junction resolutionThomas Wechsler
London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
Nature 471:642-6. 2011.... - RAD51C is required for Holliday junction processing in mammalian cellsYilun Liu
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
Science 303:243-6. 2004..We conclude that the RAD51 paralogs are involved in HJ processing in human cells... - Regulatory control of the resolution of DNA recombination intermediates during meiosis and mitosisJoao Matos
London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK
Cell 147:158-72. 2011..Mitotic regulation thereby facilitates chromosome segregation while limiting the potential for loss of heterozygosity and sister-chromatid exchanges... - Human DNA polymerase eta promotes DNA synthesis from strand invasion intermediates of homologous recombinationMichael J McIlwraith
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts, EN6 3LD, United Kingdom
Mol Cell 20:783-92. 2005..Our results indicate a dual function for poleta at stalled replication forks: the promotion of translesion synthesis and the reinitiation of DNA synthesis by homologous recombination repair... - Telomere maintenance requires the RAD51D recombination/repair proteinMadalena Tarsounas
Cancer Research UK, London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire, EN6 3LD, United Kingdom
Cell 117:337-47. 2004..We conclude that RAD51D plays a dual cellular role in both the repair of DNA double-strand breaks and telomere protection against attrition and fusion... - Involvement of human polynucleotide kinase in double-strand break repair by non-homologous end joiningClaire Chappell
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
EMBO J 21:2827-32. 2002..This work provides the first demonstration of a direct, specific role for human PNK in DSB repair... - Recombination at mammalian telomeres: an alternative mechanism for telomere protection and elongationMadalena Tarsounas
Cancer Research UK, London Research Institute, South Mimms, Herts, UK
Cell Cycle 4:672-4. 2005..Understanding the mechanisms by which HR promotes telomere maintenance has important implications for genomic stability and tumorigenesis... - RTEL1 maintains genomic stability by suppressing homologous recombinationLouise J Barber
DNA Damage Response Laboratory, London Research Institute, Cancer Research UK, Clare Hall, South Mimms EN6 3LD, UK
Cell 135:261-71. 2008..We propose that loss of HR control after deregulation of RTEL1 may be a critical event that drives genome instability and cancer... - The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediatesIvan 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... - Stabilization of RAD51 nucleoprotein filaments by the C-terminal region of BRCA2Fumiko Esashi
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK
Nat Struct Mol Biol 14:468-74. 2007..We suggest that interactions of the BRCA2 C-terminal region with RAD51 may facilitate efficient nucleation of RAD51 multimers on DNA and thereby stimulate recombination-mediated repair... - Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteinsIvan Ahel
Genetic Recombination and, Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK
Nature 451:81-5. 2008.... - DNA repair synthesis facilitates RAD52-mediated second-end capture during DSB repairMichael J McIlwraith
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK
Mol Cell 29:510-6. 2008..coli SSB. Following repair synthesis and second-end capture, de novo DNA synthesis was observed from the captured second DNA end... - Holliday junction resolution in human cells: two junction endonucleases with distinct substrate specificitiesAngelos Constantinou
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
EMBO J 21:5577-85. 2002..However, the Mus81-associated endonuclease may play a more direct role in replication fork collapse by catalysing the cleavage of stalled fork structures... - BRCA2-dependent and independent formation of RAD51 nuclear fociMadalena Tarsounas
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK
Oncogene 22:1115-23. 2003.... - Identification and characterization of the human mus81-eme1 endonucleaseAlberto Ciccia
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, United Kingdom
J Biol Chem 278:25172-8. 2003..quot; We conclude that human Mus81-Eme1 is a flap/fork endonuclease that is likely to play a role in the processing of stalled replication fork intermediates... - Conformational changes modulate the activity of human RAD51 proteinYilun Liu
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
J Mol Biol 337:817-27. 2004..These extended filaments mimic the active form of the Escherichia coli RecA-ssDNA filament that exhibits efficient strand-exchange activity... - Interactions between human BRCA2 protein and the meiosis-specific recombinase DMC1Tina Thorslund
Clare Hall Laboratories, Cancer Research UK, London Research Institute, South Mimms, Herts, UK
EMBO J 26:2915-22. 2007..These results lead us to suggest that BRCA2 is a universal regulator of RAD51/DMC1 recombinase actions... - Synthetic junctions as tools to identify and characterize Holliday junction resolvasesUlrich Rass
Cancer Research United Kingdom, London Research Institutem Clare Hall Laboratories, South Mimms, Hertfordshire
Methods Enzymol 408:485-501. 2006..Additionally, a method is described that can be used to rapidly screen a TAP-tagged library of proteins for resolvase activity without a need for conventional purification procedures... - DNA interstrand crosslink repair and cancerAndrew J Deans
London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms EN63LD, UK
Nat Rev Cancer 11:467-80. 2011..Understanding how the FA pathway links nucleases, helicases and other DNA-processing enzymes should lead to more targeted uses of ICL-inducing agents in cancer treatment and could provide novel insights into drug resistance... - Structure of the single-strand annealing domain of human RAD52 proteinMartin R Singleton
Cancer Research U K, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
Proc Natl Acad Sci U S A 99:13492-7. 2002..A large, positively charged groove runs along the surface of the ring, readily suggesting a mechanism by which RAD52 presents the single strand for reannealing with complementary single-stranded DNA... - Happy Hollidays: 40th anniversary of the Holliday junctionYilun Liu
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
Nat Rev Mol Cell Biol 5:937-44. 2004..To understand the importance of the Holliday model we must look back in the history of science beyond the last 40 years, to a time when theories of heredity were being proposed by Gregor Johann Mendel... - InTERTpreting telomerase structure and functionHaley D M Wyatt
London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, EN6 3LD, UK
Nucleic Acids Res 38:5609-22. 2010..To emphasize the physiological importance of telomeres and telomerase, we also present a general discussion of the human diseases associated with telomerase dysfunction... - Specific interaction of IP6 with human Ku70/80, the DNA-binding subunit of DNA-PKLes A Hanakahi
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
EMBO J 21:2038-44. 2002..The yeast homologue of Ku70/80, yKu70/80, fails to bind IP6, indicating that the function of IP6 in non-homologous end-joining, like that of DNA-PK(cs), is unique to the mammalian end-joining process... - Distinct functions of BRCA1 and BRCA2 in double-strand break repairYilun Liu
Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Hertfordshire, UK
Breast Cancer Res 4:9-13. 2002..In contrast, the role of BRCA2 in DNA repair may be more defined by its direct interaction with the RAD51 recombinase... - Eme1 is involved in DNA damage processing and maintenance of genomic stability in mammalian cellsJacinth Abraham
Advanced Medical Discovery Institute, Ontario Cancer Institute, 620 University Avenue, Suite 706, Toronto, Ontario M5G 2C1, Canada
EMBO J 22:6137-47. 2003..Most importantly, Eme1 deficiency led to spontaneous genomic instability. These results reveal that mammalian Eme1 plays a key role in DNA repair and the maintenance of genome integrity... - Interplay between human DNA repair proteins at a unique double-strand break in vivoAmélie Rodrigue
Genome Stability Laboratory, Laval University Cancer Research Center, Quebec City, Quebec, Canada
EMBO J 25:222-31. 2006..We propose that RAD51C ensures a tight regulation of RAD51 assembly during DSB repair and plays a direct role in repairing DSBs in vivo... - Role of mammalian RAD51L2 (RAD51C) in recombination and genetic stabilityCatherine A French
Medical Research Council, Radiation and Genome Stability Unit, Harwell, Oxfordshire OX11 0RD, United Kingdom
J Biol Chem 277:19322-30. 2002..Our results demonstrate that RAD51L2 has a key role in mammalian RAD51-dependent processes, contingent on the formation of protein complexes involved in homologous recombination repair... - RIDDLE immunodeficiency syndrome is linked to defects in 53BP1-mediated DNA damage signalingGrant S Stewart
Cancer Research UK, Institute for Cancer Studies, Birmingham University, Vincent Drive, Edgbaston, Birmingham, United Kingdom
Proc Natl Acad Sci U S A 104:16910-5. 2007..Therefore, these data indicate the existence of a DNA double-strand break-repair protein that functions upstream of 53BP1 and contributes to the normal development of the human immune system... - Direct interaction of FANCD2 with BRCA2 in DNA damage response pathwaysShobbir Hussain
Division of Genetics and Development, Guy s, King s and St Thomas s School of Medicine, King s College London, UK
Hum Mol Genet 13:1241-8. 2004..These findings suggest that FANCD2 may have a role in the cellular response to stalled replication forks or in the repair of replication-associated double-strand breaks, irrespective of the type of primary DNA lesion... - Holliday junction branch migration and resolution assaysAngelos Constantinou
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland
Methods Mol Biol 262:239-53. 2004..The use of these substrates in assays designed to detect Holliday junction branch migration and resolution activities is described... - Human RECQ5beta, a protein with DNA helicase and strand-annealing activities in a single polypeptidePatrick L Garcia
Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
EMBO J 23:2882-91. 2004..This is the first demonstration of a DNA helicase with an intrinsic DNA strand-annealing function residing in a separate domain... - RAD51C deficiency in mice results in early prophase I arrest in males and sister chromatid separation at metaphase II in femalesSergey Kuznetsov
Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA
J Cell Biol 176:581-92. 2007..Based on the marked reduction in Holliday junction (HJ) resolution activity in Rad51c-null mouse embryonic fibroblasts, we propose that this late function may be associated with HJ resolution... - Single-stranded DNA-binding protein hSSB1 is critical for genomic stabilityDerek J Richard
Signal Transduction Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia
Nature 453:677-81. 2008..These findings establish that hSSB1 influences diverse endpoints in the cellular DNA damage response... - XRCC3 and Rad51 modulate replication fork progression on damaged vertebrate chromosomesJudith 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... - BRCA2 BRC motifs bind RAD51-DNA filamentsVitold E Galkin
Department of Biochemistry and Molecular Genetics, University of Virginia Health Sciences Center, Charlottesville, VA 22908 0733, USA
Proc Natl Acad Sci U S A 102:8537-42. 2005....