Research Topics
Genomes and Genes | Jesper Q SvejstrupSummaryAffiliation: Imperial Cancer Research Fund Country: UK Publications
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Publications
Mechanisms of transcription-coupled DNA repairJesper Q Svejstrup
Imperial Cancer Research Fund, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, UK
Nat Rev Mol Cell Biol 3:21-9. 2002..In this review, our knowledge of eukaryotic transcription-coupled repair (TCR) will be considered from the point of view of transcription, and current models for the mechanism of TCR will be discussed...
An iron-sulfur cluster domain in Elp3 important for the structural integrity of elongatorCatherine Greenwood
Clare Hall Laboratories, Cancer Research UK London Research Institute, Blanche Lane, South Mimms EN6 3LD, United Kingdom
J Biol Chem 284:141-9. 2009..Together our data support the idea that the Elp3 FeS cluster is essential for normal Elongator function in vivo primarily as a structural, rather than catalytic, domain...
Distinct ubiquitin ligases act sequentially for RNA polymerase II polyubiquitylationMichelle Harreman
Mechanisms of Transcription Laboratory, Clare Hall Laboratories, Cancer Research UK London Research Institute, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, United Kingdom
Proc Natl Acad Sci U S A 106:20705-10. 2009....
Multiple mechanisms confining RNA polymerase II ubiquitylation to polymerases undergoing transcriptional arrestBaggavalli P Somesh
Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Herts EN6 3LD, United Kingdom
Cell 121:913-23. 2005..These results identify several mechanisms that confine ubiquitylation of RNAPII to the forms of the enzyme that arrest during elongation...
An rtt109-independent role for vps75 in transcription-associated nucleosome dynamicsLuke A Selth
Clare Hall Laboratories, Cancer Research UK London Research Institute, Blanche Lane, South Mimms, Hertfordshire, U K
Mol Cell Biol 29:4220-34. 2009..These results indicate a role for Vps75 in nucleosome dynamics during transcription, and importantly, this function appears to be largely independent of Rtt109...
Communication between distant sites in RNA polymerase II through ubiquitylation factors and the polymerase CTDBaggavalli P Somesh
Mechanisms of Transcription Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, UK
Cell 129:57-68. 2007..These data reveal the specificity and mechanism of RNAPII ubiquitylation and demonstrate that E2s can play a crucial role in substrate recognition...
A ubiquitin-binding domain in Cockayne syndrome B required for transcription-coupled nucleotide excision repairRoy Anindya
Clare Hall Laboratories, Cancer Research UK London Research Institute, Blanche Lane, South Mimms EN6 3LD, UK
Mol Cell 38:637-48. 2010..Together, our results indicate an essential role for protein ubiquitylation and CSB's UBD in triggering damage incision during TC-NER and allow us to integrate the function of CSA and CSB in a model for the process...
GTP-dependent binding and nuclear transport of RNA polymerase II by Npa3 proteinLidija Staresincic
Mechanisms of Transcription Laboratory, Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms EN6 3LD, UK
J Biol Chem 286:35553-61. 2011..Together, our data suggest that Npa3 defines an unconventional pathway for nuclear import of RNAPII, which involves GTP-dependent binding of Npa3 to the polymerase...
Reversal of RNA polymerase II ubiquitylation by the ubiquitin protease Ubp3Kristian Kvint
Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Herts EN6 3LD, UK
Mol Cell 30:498-506. 2008..In agreement with this, cells with compromised DNA repair are better equipped to survive UV damage when UPB3 is deleted...
Physical and functional interaction between Elongator and the chromatin-associated Kti12 proteinThodoris G Petrakis
Cancer Research UK London Research Institute, Clare Hall Laboratories, Hertfordshire, UK
J Biol Chem 280:19454-60. 2005..Together, these experiments indicate a close physical and functional relationship between Elongator and the highly conserved Kti12 protein...
Molecular architecture, structure-function relationship, and importance of the Elp3 subunit for the RNA binding of holo-elongatorThodoris G Petrakis
Cancer Research UK, London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, United Kingdom
J Biol Chem 279:32087-92. 2004..In contrast, Elongator-RNA interaction requires the Elp3 protein. Together, these data shed light on the structure-function relationship of the Elongator complex...
DNA damage-induced Def1-RNA polymerase II interaction and Def1 requirement for polymerase ubiquitylation in vitroJames Reid
Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, United Kingdom
J Biol Chem 279:29875-8. 2004..These results support a model in which Def1 interacts with RNAPII in response to DNA damage, recruiting the ubiquitylation machinery to enable its modification and subsequent degradation...
Spreading of Sir3 protein in cells with severe histone H3 hypoacetylationArnold Kristjuhan
Mechanisms of Transcription Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, United Kingdom
Proc Natl Acad Sci U S A 100:7551-6. 2003..Interestingly, growth defects caused by gcn5 elp3 mutation can be suppressed by SIR deletion, suggesting that Sir proteins become detrimental for growth when chromatin is severely hypoacetylated...
Evidence for distinct mechanisms facilitating transcript elongation through chromatin in vivoArnold Kristjuhan
Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
EMBO J 23:4243-52. 2004....
Evidence that transcript cleavage is essential for RNA polymerase II transcription and cell viabilityStefan Sigurdsson
Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms, UK
Mol Cell 38:202-10. 2010..Our results suggest that transcription problems leading to backtracking are frequent in vivo and that reactivation of backtracked RNAPII is crucial for transcription...
Transcription. Histones face the FACTJesper Q Svejstrup
Cancer Research, London Research Institute, Clare Hall Laboratories, Hertfordshire, UK
Science 301:1053-5. 2003
Interaction of Fcp1 phosphatase with elongating RNA polymerase II holoenzyme, enzymatic mechanism of action, and genetic interaction with elongatorStephanie E Kong
Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, EN6 3LD, United Kingdom
J Biol Chem 280:4299-306. 2005..Together, these results shed new light on mechanisms that drive the transcription cycle and point to a role for Fcp1 in the recycling of RNAPII after dissociation from active genes...
Hyperphosphorylation of the C-terminal repeat domain of RNA polymerase II facilitates dissociation of its complex with mediatorT Max M Søgaard
Clare Hall Laboratories, Cancer Research UK London Research Institute, Blanche Lane, South Mimms, UK
J Biol Chem 282:14113-20. 2007..These data shed new light on mechanisms that drive the RNAPII transcription cycle and suggest a mechanism for the enhancement of CTD kinase activity by the Mediator complex...
Transcriptional inhibition of genes with severe histone h3 hypoacetylation in the coding regionArnold Kristjuhan
Mechanisms of Transcription Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, EN6 3LD, Hertfordshire, United Kingdom
Mol Cell 10:925-33. 2002..These data provide insights into the effects of histone H3 hypoacetylation in vivo and underscore the importance of the overall charge of the histone tail for transcription...
Damage-induced ubiquitylation of human RNA polymerase II by the ubiquitin ligase Nedd4, but not Cockayne syndrome proteins or BRCA1Roy Anindya
Clare Hall Laboratories, Cancer Research UK London Research Institute, Blanche Lane, South Mimms EN6 3LD, UK
Mol Cell 28:386-97. 2007..Nedd4-dependent RNAPII ubiquitylation could also be reconstituted with highly purified proteins. Together, our results indicate that transcriptional arrest at DNA lesions triggers Nedd4 recruitment and RNAPII ubiquitylation...
Elongator interactions with nascent mRNA revealed by RNA immunoprecipitationChristopher Gilbert
Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, United Kingdom
Mol Cell 14:457-64. 2004..These results strongly support a role for Elongator in transcript elongation...
Elongator is a histone H3 and H4 acetyltransferase important for normal histone acetylation levels in vivoG Sebastiaan Winkler
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, United Kingdom
Proc Natl Acad Sci U S A 99:3517-22. 2002..By using chromatin immunoprecipitation, we show that the levels of multiply acetylated histone H3 and H4 in chromatin are decreased in vivo in yeast cells lacking ELP3...
Isolation and mass spectrometry of transcription factor complexesG Sebastiaan Winkler
Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, EN6 3LD, Hertfordshire, UK
Methods 26:260-9. 2002..As an example, we provide the procedures used to isolate and analyze yeast Elongator, a histone acetyltransferase complex important for transcript elongation, which led to the identification of three novel subunits...
A role for checkpoint kinase-dependent Rad26 phosphorylation in transcription-coupled DNA repair in Saccharomyces cerevisiaeMichael Taschner
Clare Hall Laboratories, Cancer Research UK London Research Institute, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, United Kingdom
Mol Cell Biol 30:436-46. 2010..These findings establish a direct role for Mec1 kinase in transcription-coupled repair, at least partly via phosphorylation of Rad26, the main transcription-repair coupling factor...
Stability, flexibility, and dynamic interactions of colliding RNA polymerase II elongation complexesHideaki Saeki
Mechanisms of Transcription Laboratory, Clare Hall Laboratories, Cancer Research UK London Research Institute, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, UK
Mol Cell 35:191-205. 2009....
Transcript Elongation by RNA Polymerase IILuke A Selth
Mechanisms of Transcription Laboratory, Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms, Hertfordshire EN6 3LD, United Kingdom
Annu Rev Biochem 79:271-93. 2010..This review addresses basic aspects of transcript elongation by RNA polymerase II (RNAPII) and how it relates to other DNA-related processes...
Direct inhibition of RNA polymerase II transcription by RECQL5Ozan Aygün
Mechanisms of Transcription Laboratory, Clare Hall Laboratories, Cancer Research UK, London Research Institute, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, United Kingdom
J Biol Chem 284:23197-203. 2009..Indeed, RECQL5 helicase activity is not required for inhibition. We discuss our findings in light of the fact that RECQ5(-/-) mice have elevated levels of DNA recombination and a higher incidence of cancer...
Incision of a 1,3-intrastrand d(GpTpG)-cisplatin adduct by nucleotide excision repair proteins from yeastStephanie E Kong
Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire, UK
DNA Repair (Amst) 1:731-41. 2002....
Elongator complex: how many roles does it play?Jesper Q Svejstrup
Clare Hall Laboratories, Cancer Research UK London Research Institute, Blanche Lane, South Mimms, EN6 3LD, UK
Curr Opin Cell Biol 19:331-6. 2007..One of the subunits of Elongator is encoded by a gene that is mutated in patients suffering from the severe neurodevelopmental disorder familial dysautonomia...
RNA polymerase II collision interrupts convergent transcriptionDavid J Hobson
Mechanisms of Transcription Laboratory, Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms, London EN6 3LD, UK
Mol Cell 48:365-74. 2012..These results provide insight into fundamental mechanisms of gene traffic control and point to an unexplored effect of antisense transcription on gene regulation via polymerase collision...
The interface between transcription and mechanisms maintaining genome integrityJesper Q Svejstrup
Clare Hall Laboratories, Cancer Research UK London Research Institute, Blanche Lane, South Mimms, EN6 3LD, UK
Trends Biochem Sci 35:333-8. 2010..This review provides an overview of our present knowledge of how eukaryotic RNA polymerase II transcription affects, and is affected by, other DNA-related processes such as chromatin remodeling, DNA repair, recombination and replication...
A Rad26-Def1 complex coordinates repair and RNA pol II proteolysis in response to DNA damageElies C Woudstra
Mechanisms of Gene Transcription Laboratory, Cancer Research UK, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, UK
Nature 415:929-33. 2002....
Contending with transcriptional arrest during RNAPII transcript elongationJesper Q Svejstrup
Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms, London EN6 3LD, UK
Trends Biochem Sci 32:165-71. 2007..In particular, studies of RNAPII ubiquitylation and degradation have provided new insight into how cells handle obstacle-induced transcriptional arrest...
Ubiquitylation and degradation of elongating RNA polymerase II: the last resortMarcus D Wilson
Mechanisms of Transcription Laboratory, Cancer Research UK London Research Institute, South Mimms, UK
Biochim Biophys Acta 1829:151-7. 2013..In this review, we describe the mechanisms and factors responsible for the last resort mechanism of transcriptional elongation. This article is part of a Special Issue entitled: RNA polymerase II Transcript Elongation...
DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongationPierre Close
Mechanisms of Transcription Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK
Nature 484:386-9. 2012..Together, these data indicate that the DBIRD complex acts at the interface between mRNP particles and RNAPII, integrating transcript elongation with the regulation of alternative splicing...
An assay for studying ubiquitylation of RNA polymerase II and other proteins in crude yeast extractsJames Reid
Cancer Research United Kingdom, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire
Methods Enzymol 408:264-73. 2006..These procedures, combined with the ease of genetic manipulations in yeast, provide a new powerful tool for investigating the mechanisms underlying protein ubiquitylation...
Rescue of arrested RNA polymerase II complexesJesper Q Svejstrup
Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
J Cell Sci 116:447-51. 2003..However, when this action is not possible and Pol II is left irreversibly trapped on DNA, the polymerase is instead ubiquitylated and eventually removed by proteolysis...
RNA immunoprecipitation for determining RNA-protein associations in vivoChris Gilbert
Cancer Research UK, London Research Institute, Clare Hall Laboratories, Hertfordshire, UK
Curr Protoc Mol Biol . 2006..This unit describes the RIP procedure for Saccharomyces cerevisiae. Although the corresponding steps for metazoan cells have not yet been worked out, it is likely that the yeast procedure can easily be adapted for use in other organisms...
Vps75, a new yeast member of the NAP histone chaperone familyLuke Selth
Clare Hall Laboratories, Cancer Research UK London Research Institute, Blanche Lane, South Mimms, EN6 3LD, United Kingdom
J Biol Chem 282:12358-62. 2007....
The RNA polymerase II transcription cycle: cycling through chromatinJesper Q Svejstrup
Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire, EN6 3LD, UK
Biochim Biophys Acta 1677:64-73. 2004..This review gives a brief overview of the transcription cycle as a whole, focusing especially on selected mechanisms that may drive or restrict the cycle, and on how the presence of chromatin may influence these mechanisms...
Chromatin elongation factorsJesper Q Svejstrup
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
Curr Opin Genet Dev 12:156-61. 2002..Insights into the function of these factors have been gained by a combination of yeast genetics and biochemical studies in mammalian systems...
Transcription repair coupling factor: a very pushy enzymeJesper Q Svejstrup
Cancer Research UK London Research Institute, Clare Hall Laboratory, South Mimms, EN6 3LD, UK
Mol Cell 9:1151-2. 2002..A recent study of the bacterial Mfd protein (Park et al., 2002 [Cell volume 109]) provides new insight into mechanisms that release RNAP from sites of arrest such as noncoding DNA lesions...
RNA polymerase II: a "nobel" enzyme demystifiedJesper Q Svejstrup
Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, EN6 3LD, United Kingdom
Mol Cell 24:637-42. 2006
Purification of elongating RNA polymerase II and other factors from yeast chromatinJesper Q Svejstrup
London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, United Kingdom
Methods Enzymol 371:491-8. 2003
RECQL5 helicase: connections to DNA recombination and RNA polymerase II transcriptionOzan Aygün
Mechanisms of Transcription Laboratory, Clare Hall Laboratories, Cancer Research UK London Research Institute, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, United Kingdom
DNA Repair (Amst) 9:345-53. 2010..Here, we describe the possible implications of recent studies and discuss models for RECQL5 function...
Transcription: another mark in the tailJesper Q Svejstrup
Mechanisms of Transcription Laboratory, Cancer Research UK London Research Institute, South Mimms, UK
EMBO J 31:2753-4. 2012..While important functions for Ser(2)-, Ser(5)-, and Ser(7)-phosphorylation have previously been described, a new report in The EMBO Journal now suggests an unexpectedly crucial role for Thr(4) phosphorylation as well...
RNA Immunoprecipitation to Determine RNA-Protein Associations In VivoLuke A Selth
Mechanisms of Gene Transcription Laboratory, Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms, Hertfordshire EN6 3LD, UK
CSH Protoc 2009:pdb.prot5234. 2009..The basics of RIP are very similar to chromatin immunoprecipitation (ChIP), but with some caveats that are important to appreciate to take full advantage of the possibilities afforded by RIP...
Purification and characterization of the human elongator complexNicola A Hawkes
Mechanisms of Gene Transcription Laboratory, Imperial Cancer Research Fund Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire, EN6 3LD, United Kingdom
J Biol Chem 277:3047-52. 2002..Mutations in IKAP can result in the severe human disorder familial dysautonomia, raising the possibility that this disease might be due to compromised Elongator function and therefore could be a transcription disorder...
Transcription impairment and cell migration defects in elongator-depleted cells: implication for familial dysautonomiaPierre Close
Laboratory of Medical Chemistry and Human Genetics, Center for Biomedical Integrative Genoproteomics, University of Liege, Belgium
Mol Cell 22:521-31. 2006..These results indicate that defects in Elongator function affect transcriptional elongation of several genes and that the ensuing cell motility deficiencies may underlie the neuropathology of FD patients...
The NC2 alpha and beta subunits play different roles in vivoSandrine Creton
, CMU, Geneva 4, Switzerland
Genes Dev 16:3265-76. 2002..Thus, the separation of NC2 alpha and beta function indicated by these mutants also supports the existence of multiple NC2 complexes with different functions in transcription...
A role for noncoding transcription in activation of the yeast PHO5 geneJay P Uhler
Mechanisms of Transcription Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms EN6 3LD, United Kingdom
Proc Natl Acad Sci U S A 104:8011-6. 2007..We propose that noncoding transcription through positioned nucleosomes can enhance chromatin plasticity so that chromatin remodeling and activation of traversed genes occur in a timely manner...
