Cramer, Patrick

[["dc.bibliographiccitation.firstpage","2093"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Genes & Development"],["dc.bibliographiccitation.lastpage","2105"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Blattner, C."],["dc.contributor.author","Jennebach, S."],["dc.contributor.author","Herzog, F."],["dc.contributor.author","Mayer, A."],["dc.contributor.author","Cheung, A. C. M."],["dc.contributor.author","Witte, G."],["dc.contributor.author","Lorenzen, K."],["dc.contributor.author","Hopfner, K.-P."],["dc.contributor.author","Heck, A. J. R."],["dc.contributor.author","Aebersold, R."],["dc.contributor.author","Cramer, P."],["dc.date.accessioned","2017-09-07T11:43:22Z"],["dc.date.available","2017-09-07T11:43:22Z"],["dc.date.issued","2011"],["dc.description.abstract","Cell growth is regulated during RNA polymerase (Pol) I transcription initiation by the conserved factor Rrn3/TIF-IA in yeast/humans. Here we provide a structure-function analysis of Rrn3 based on a combination of structural biology with in vivo and in vitro functional assays. The Rrn3 crystal structure reveals a unique HEAT repeat fold and a surface serine patch. Phosphorylation of this patch represses human Pol I transcription, and a phospho-mimetic patch mutation prevents Rrn3 binding to Pol I in vitro and reduces cell growth and Pol I gene occupancy in vivo. Cross-linking indicates that Rrn3 binds Pol I between its subcomplexes, AC40/19 and A14/43, which faces the serine patch. The corresponding region of Pol II binds the Mediator head that cooperates with transcription factor (TF) IIB. Consistent with this, the Rrn3-binding factor Rrn7 is predicted to be a TFIIB homolog. This reveals the molecular basis of Rrn3-regulated Pol I initiation and cell growth, and indicates a general architecture of eukaryotic transcription initiation complexes."],["dc.identifier.doi","10.1101/gad.17363311"],["dc.identifier.gro","3142659"],["dc.identifier.isi","000295775600009"],["dc.identifier.pmid","21940764"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0890-9369"],["dc.title","Molecular basis of Rrn3-regulated RNA polymerase I initiation and cell growth"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Systems Biology"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Shao, Rui"],["dc.contributor.author","Kumar, Banushree"],["dc.contributor.author","Lidschreiber, Katja"],["dc.contributor.author","Lidschreiber, Michael"],["dc.contributor.author","Cramer, Patrick"],["dc.contributor.author","Elsässer, Simon J"],["dc.date.accessioned","2022-03-01T11:44:18Z"],["dc.date.available","2022-03-01T11:44:18Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.15252/msb.202110407"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/102989"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","1744-4292"],["dc.relation.issn","1744-4292"],["dc.title","Distinct transcription kinetics of pluripotent cell states"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","17446"],["dc.bibliographiccitation.issue","25"],["dc.bibliographiccitation.journal","Journal of biological chemistry"],["dc.bibliographiccitation.lastpage","17452"],["dc.bibliographiccitation.volume","289"],["dc.contributor.author","Schulz, D."],["dc.contributor.author","Pirkl, N."],["dc.contributor.author","Lehmann, E."],["dc.contributor.author","Cramer, P."],["dc.date.accessioned","2017-09-07T11:46:12Z"],["dc.date.available","2017-09-07T11:46:12Z"],["dc.date.issued","2014"],["dc.description.abstract","RNA polymerase II (Pol II) is the central enzyme that carries out eukaryotic mRNA transcription and consists of a 10-subunit catalytic core and a subcomplex of subunits Rpb4 and Rpb7 (Rpb4/7). Rpb4/7 has been proposed to dissociate from Pol II, enter the cytoplasm, and function there in mRNA translation and degradation. Here we provide evidence that Rpb4 mainly functions in nuclear mRNA synthesis by Pol II, as well as evidence arguing against an important cytoplasmic role in mRNA degradation. We used metabolic RNA labeling and comparative Dynamic Transcriptome Analysis to show that Rpb4 deletion in Saccharomyces cerevisiae causes a drastic defect in mRNA synthesis that is compensated by down-regulation of mRNA degradation, resulting in mRNA level buffering. Deletion of Rpb4 can be rescued by covalent fusion of Rpb4 to the Pol II core subunit Rpb2, which largely restores mRNA synthesis and degradation defects caused by Rpb4 deletion. Thus, Rpb4 is a bona fide Pol II core subunit that functions mainly in mRNA synthesis."],["dc.identifier.doi","10.1074/jbc.M114.568014"],["dc.identifier.gro","3142103"],["dc.identifier.isi","000338018100013"],["dc.identifier.pmid","24802753"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4578"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1083-351X"],["dc.relation.issn","0021-9258"],["dc.title","Rpb4 Subunit Functions Mainly in mRNA Synthesis by RNA Polymerase II"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Nature Structural & Molecular Biology"],["dc.contributor.author","Kabinger, Florian"],["dc.contributor.author","Stiller, Carina"],["dc.contributor.author","Schmitzová, Jana"],["dc.contributor.author","Dienemann, C."],["dc.contributor.author","Kokic, Goran"],["dc.contributor.author","Hillen, Hauke S."],["dc.contributor.author","Höbartner, Claudia"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2021-09-01T06:42:22Z"],["dc.date.available","2021-09-01T06:42:22Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Molnupiravir is an orally available antiviral drug candidate currently in phase III trials for the treatment of patients with COVID-19. Molnupiravir increases the frequency of viral RNA mutations and impairs SARS-CoV-2 replication in animal models and in humans. Here, we establish the molecular mechanisms underlying molnupiravir-induced RNA mutagenesis by the viral RNA-dependent RNA polymerase (RdRp). Biochemical assays show that the RdRp uses the active form of molnupiravir, β- d - N 4 -hydroxycytidine (NHC) triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate. When the RdRp uses the resulting RNA as a template, NHC directs incorporation of either G or A, leading to mutated RNA products. Structural analysis of RdRp–RNA complexes that contain mutagenesis products shows that NHC can form stable base pairs with either G or A in the RdRp active center, explaining how the polymerase escapes proofreading and synthesizes mutated RNA. This two-step mutagenesis mechanism probably applies to various viral polymerases and can explain the broad-spectrum antiviral activity of molnupiravir."],["dc.identifier.doi","10.1038/s41594-021-00651-0"],["dc.identifier.pii","651"],["dc.identifier.pmid","34381216"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89038"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/381"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/171"],["dc.identifier.url","https://for2848.gwdguser.de/literature/publications/28"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-455"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","FOR 2848: Architektur und Heterogenität der inneren mitochondrialen Membran auf der Nanoskala"],["dc.relation","FOR 2848 | St01: Structure and distribution of ribosomes at the inner mitochondrial membrane"],["dc.relation.eissn","1545-9985"],["dc.relation.issn","1545-9993"],["dc.relation.workinggroup","RG Cramer"],["dc.relation.workinggroup","RG Hillen (Structure and Function of Molecular Machines)"],["dc.rights","CC BY 4.0"],["dc.title","Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1401"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Genes & Development"],["dc.bibliographiccitation.lastpage","1415"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Meinhart, Anton"],["dc.contributor.author","Kamenski, Tomislav"],["dc.contributor.author","Hoeppner, Sabine"],["dc.contributor.author","Baumli, Sonja"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2018-03-08T09:22:16Z"],["dc.date.available","2018-03-08T09:22:16Z"],["dc.date.issued","2005"],["dc.description.abstract","The C-terminal domain (CTD) of RNA polymerase II (Pol II) integrates nuclear events by binding proteins involved in mRNA biogenesis. CTD-binding proteins recognize a specific CTD phosphorylation pattern, which changes during the transcription cycle, due to the action of CTD-modifying enzymes. Structural and functional studies of CTD-binding and -modifying proteins now reveal some of the mechanisms underlying CTD function. Proteins recognize CTD phosphorylation patterns either directly, by contacting phosphorylated residues, or indirectly, without contact to the phosphate. The catalytic mechanisms of CTD kinases and phosphatases are known, but the basis for CTD specificity of these enzymes remains to be understood."],["dc.identifier.doi","10.1101/gad.1318105"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/12924"],["dc.language.iso","en"],["dc.notes.intern","GRO-Li-Import"],["dc.notes.status","final"],["dc.relation.doi","10.1101/gad.1318105"],["dc.relation.issn","0890-9369"],["dc.relation.issn","0890-9369"],["dc.title","A structural perspective of CTD function"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","120"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cell"],["dc.bibliographiccitation.lastpage","131"],["dc.bibliographiccitation.volume","169"],["dc.contributor.author","Engel, Christoph"],["dc.contributor.author","Gubbey, Tobias"],["dc.contributor.author","Neyer, Simon"],["dc.contributor.author","Sainsbury, Sarah"],["dc.contributor.author","Oberthuer, Christiane"],["dc.contributor.author","Baejen, Carlo"],["dc.contributor.author","Bernecky, Carrie"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2018-01-09T13:23:49Z"],["dc.date.available","2018-01-09T13:23:49Z"],["dc.date.issued","2017"],["dc.description.abstract","Transcription initiation at the ribosomal RNA promoter requires RNA polymerase (Pol) I and the initiation factors Rrn3 and core factor (CF). Here, we combine X-ray crystallography and cryo-electron microscopy (cryo-EM) to obtain a molecular model for basal Pol I initiation. The three-subunit CF binds upstream promoter DNA, docks to the Pol I-Rrn3 complex, and loads DNA into the expanded active center cleft of the polymerase. DNA unwinding between the Pol I protrusion and clamp domains enables cleft contraction, resulting in an active Pol I conformation and RNA synthesis. Comparison with the Pol II system suggests that promoter specificity relies on a distinct \"bendability\" and \"meltability\" of the promoter sequence that enables contacts between initiation factors, DNA, and polymerase."],["dc.identifier.doi","10.1016/j.cell.2017.03.003"],["dc.identifier.pmid","28340337"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11592"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1097-4172"],["dc.title","Structural Basis of RNA Polymerase I Transcription Initiation"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","14861"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Wittmann, Sina"],["dc.contributor.author","Renner, Max"],["dc.contributor.author","Watts, Beth R."],["dc.contributor.author","Adams, Oliver"],["dc.contributor.author","Huseyin, Miles"],["dc.contributor.author","Baejen, Carlo"],["dc.contributor.author","El Omari, Kamel"],["dc.contributor.author","Kilchert, Cornelia"],["dc.contributor.author","Heo, Dong-Hyuk"],["dc.contributor.author","Kecman, Tea"],["dc.contributor.author","Cramer, Patrick"],["dc.contributor.author","Grimes, Jonathan M."],["dc.contributor.author","Vasiljeva, Lidia"],["dc.date.accessioned","2018-01-09T13:04:55Z"],["dc.date.available","2018-01-09T13:04:55Z"],["dc.date.issued","2017"],["dc.description.abstract","Termination of RNA polymerase II (Pol II) transcription is an important step in the transcription cycle, which involves the dislodgement of polymerase from DNA, leading to release of a functional transcript. Recent studies have identified the key players required for this process and showed that a common feature of these proteins is a conserved domain that interacts with the phosphorylated C-terminus of Pol II (CTD-interacting domain, CID). However, the mechanism by which transcription termination is achieved is not understood. Using genome-wide methods, here we show that the fission yeast CID-protein Seb1 is essential for termination of protein-coding and non-coding genes through interaction with S2-phosphorylated Pol II and nascent RNA. Furthermore, we present the crystal structures of the Seb1 CTD- and RNA-binding modules. Unexpectedly, the latter reveals an intertwined two-domain arrangement of a canonical RRM and second domain. These results provide important insights into the mechanism underlying eukaryotic transcription termination."],["dc.identifier.doi","10.1038/ncomms14861"],["dc.identifier.pmid","28367989"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11591"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","2041-1723"],["dc.title","The conserved protein Seb1 drives transcription termination by binding RNA polymerase II and nascent RNA"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","943"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Cell"],["dc.bibliographiccitation.lastpage","944"],["dc.bibliographiccitation.volume","153"],["dc.contributor.author","Michel, M."],["dc.contributor.author","Cramer, P."],["dc.date.accessioned","2017-09-07T11:47:41Z"],["dc.date.available","2017-09-07T11:47:41Z"],["dc.date.issued","2013"],["dc.description.abstract","Gene expression is largely regulated during the initiation of RNA polymerase II (PolII) transcription. In this issue, Kouzine et al. show that control of DNA melting is one of the critical rate-limiting steps for productive mRNA elongation. We discuss these findings in the context of other key energetic transitions."],["dc.identifier.doi","10.1016/j.cell.2013.04.050"],["dc.identifier.gro","3142350"],["dc.identifier.isi","000319456800003"],["dc.identifier.pmid","23706732"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7308"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0092-8674"],["dc.title","Transitions for Regulating Early Transcription"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","letter_note"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","285a"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","102"],["dc.contributor.author","Treutlein, Barbara"],["dc.contributor.author","Muschielok, Adam"],["dc.contributor.author","Andrecka, Joanna"],["dc.contributor.author","Jawhari, Anass"],["dc.contributor.author","Buchen, Claudia"],["dc.contributor.author","Kostrewa, Dirk"],["dc.contributor.author","Hög, Friederike"],["dc.contributor.author","Cramer, Patrick"],["dc.contributor.author","Michaelis, Jens"],["dc.date.accessioned","2022-03-01T11:44:54Z"],["dc.date.available","2022-03-01T11:44:54Z"],["dc.date.issued","2012"],["dc.identifier.doi","10.1016/j.bpj.2011.11.1574"],["dc.identifier.pii","S0006349511029225"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103156"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0006-3495"],["dc.title","Dynamic Architecture of the RNA Polymerase II Open Promoter Complex"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","15741"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Xu, Youwei"],["dc.contributor.author","Bernecky, Carrie"],["dc.contributor.author","Lee, Chung-Tien"],["dc.contributor.author","Maier, Kerstin C."],["dc.contributor.author","Schwalb, Bjorn"],["dc.contributor.author","Tegunov, Dimitry"],["dc.contributor.author","Plitzko, Jürgen M."],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2018-01-09T12:53:55Z"],["dc.date.available","2018-01-09T12:53:55Z"],["dc.date.issued","2017"],["dc.description.abstract","The conserved polymerase-associated factor 1 complex (Paf1C) plays multiple roles in chromatin transcription and genomic regulation. Paf1C comprises the five subunits Paf1, Leo1, Ctr9, Cdc73 and Rtf1, and binds to the RNA polymerase II (Pol II) transcription elongation complex (EC). Here we report the reconstitution of Paf1C from Saccharomyces cerevisiae, and a structural analysis of Paf1C bound to a Pol II EC containing the elongation factor TFIIS. Cryo-electron microscopy and crosslinking data reveal that Paf1C is highly mobile and extends over the outer Pol II surface from the Rpb2 to the Rpb3 subunit. The Paf1-Leo1 heterodimer and Cdc73 form opposite ends of Paf1C, whereas Ctr9 bridges between them. Consistent with the structural observations, the initiation factor TFIIF impairs Paf1C binding to Pol II, whereas the elongation factor TFIIS enhances it. We further show that Paf1C is globally required for normal mRNA transcription in yeast. These results provide a three-dimensional framework for further analysis of Paf1C function in transcription through chromatin."],["dc.identifier.doi","10.1038/ncomms15741"],["dc.identifier.pmid","28585565"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11589"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","2041-1723"],["dc.title","Architecture of the RNA polymerase II-Paf1C-TFIIS transcription elongation complex"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]