Cramer, Patrick

[["dc.bibliographiccitation.firstpage","382"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Nature Structural & Molecular Biology"],["dc.bibliographiccitation.lastpage","387"],["dc.bibliographiccitation.volume","28"],["dc.contributor.author","Farnung, Lucas"],["dc.contributor.author","Ochmann, Moritz"],["dc.contributor.author","Engeholm, Maik"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2022-02-22T12:16:36Z"],["dc.date.available","2022-02-22T12:16:36Z"],["dc.date.issued","2021"],["dc.description.abstract","Efficient transcription of RNA polymerase II (Pol II) through nucleosomes requires the help of various factors. Here we show biochemically that Pol II transcription through a nucleosome is facilitated by the chromatin remodeler Chd1 and the histone chaperone FACT when the elongation factors Spt4/5 and TFIIS are present. We report cryo-EM structures of transcribing Saccharomyces cerevisiae Pol II-Spt4/5-nucleosome complexes with bound Chd1 or FACT. In the first structure, Pol II transcription exposes the proximal histone H2A-H2B dimer that is bound by Spt5. Pol II has also released the inhibitory DNA-binding region of Chd1 that is poised to pump DNA toward Pol II. In the second structure, Pol II has generated a partially unraveled nucleosome that binds FACT, which excludes Chd1 and Spt5. These results suggest that Pol II progression through a nucleosome activates Chd1, enables FACT binding and eventually triggers transfer of FACT together with histones to upstream DNA."],["dc.identifier.doi","10.1038/s41594-021-00578-6"],["dc.identifier.pmid","33846633"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/100171"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/267"],["dc.language.iso","en"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1545-9985"],["dc.relation.issn","1545-9993"],["dc.relation.workinggroup","RG Cramer"],["dc.rights","CC BY 4.0"],["dc.title","Structural basis of nucleosome transcription mediated by Chd1 and FACT"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","279"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Kokic, Goran"],["dc.contributor.author","Hillen, Hauke S."],["dc.contributor.author","Tegunov, Dimitry"],["dc.contributor.author","Dienemann, Christian"],["dc.contributor.author","Seitz, Florian"],["dc.contributor.author","Schmitzova, Jana"],["dc.contributor.author","Farnung, Lucas"],["dc.contributor.author","Siewert, Aaron"],["dc.contributor.author","Höbartner, Claudia"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2021-08-12T07:44:55Z"],["dc.date.available","2021-08-12T07:44:55Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Remdesivir is the only FDA-approved drug for the treatment of COVID-19 patients. The active form of remdesivir acts as a nucleoside analog and inhibits the RNA-dependent RNA polymerase (RdRp) of coronaviruses including SARS-CoV-2. Remdesivir is incorporated by the RdRp into the growing RNA product and allows for addition of three more nucleotides before RNA synthesis stalls. Here we use synthetic RNA chemistry, biochemistry and cryo-electron microscopy to establish the molecular mechanism of remdesivir-induced RdRp stalling. We show that addition of the fourth nucleotide following remdesivir incorporation into the RNA product is impaired by a barrier to further RNA translocation. This translocation barrier causes retention of the RNA 3ʹ-nucleotide in the substrate-binding site of the RdRp and interferes with entry of the next nucleoside triphosphate, thereby stalling RdRp. In the structure of the remdesivir-stalled state, the 3ʹ-nucleotide of the RNA product is matched and located with the template base in the active center, and this may impair proofreading by the viral 3ʹ-exonuclease. These mechanistic insights should facilitate the quest for improved antivirals that target coronavirus replication."],["dc.identifier.doi","10.1038/s41467-020-20542-0"],["dc.identifier.pii","20542"],["dc.identifier.pmid","33436624"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/88330"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/113"],["dc.identifier.url","https://for2848.gwdguser.de/literature/publications/17"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-448"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["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","2041-1723"],["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 SARS-CoV-2 polymerase stalling by remdesivir"],["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","3232"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Oberbeckmann, Elisa"],["dc.contributor.author","Niebauer, Vanessa"],["dc.contributor.author","Watanabe, Shinya"],["dc.contributor.author","Farnung, Lucas"],["dc.contributor.author","Moldt, Manuela"],["dc.contributor.author","Schmid, Andrea"],["dc.contributor.author","Cramer, Patrick"],["dc.contributor.author","Peterson, Craig L."],["dc.contributor.author","Eustermann, Sebastian"],["dc.contributor.author","Hopfner, Karl-Peter"],["dc.contributor.author","Korber, Philipp"],["dc.date.accessioned","2022-02-22T12:16:40Z"],["dc.date.available","2022-02-22T12:16:40Z"],["dc.date.issued","2021"],["dc.description.abstract","Arrays of regularly spaced nucleosomes dominate chromatin and are often phased by alignment to reference sites like active promoters. How the distances between nucleosomes (spacing), and between phasing sites and nucleosomes are determined remains unclear, and specifically, how ATP-dependent chromatin remodelers impact these features. Here, we used genome-wide reconstitution to probe how Saccharomyces cerevisiae ATP-dependent remodelers generate phased arrays of regularly spaced nucleosomes. We find that remodelers bear a functional element named the 'ruler' that determines spacing and phasing in a remodeler-specific way. We use structure-based mutagenesis to identify and tune the ruler element residing in the Nhp10 and Arp8 modules of the INO80 remodeler complex. Generally, we propose that a remodeler ruler regulates nucleosome sliding direction bias in response to (epi)genetic information. This finally conceptualizes how remodeler-mediated nucleosome dynamics determine stable steady-state nucleosome positioning relative to other nucleosomes, DNA bound factors, DNA ends and DNA sequence elements."],["dc.identifier.doi","10.1038/s41467-021-23015-0"],["dc.identifier.pmid","34050140"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/100172"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/277"],["dc.language.iso","en"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.issn","2041-1723"],["dc.relation.workinggroup","RG Cramer"],["dc.rights","CC BY 4.0"],["dc.title","Ruler elements in chromatin remodelers set nucleosome array spacing and phasing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Farnung, Lucas"],["dc.contributor.author","Ochmann, Moritz"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2022-02-21T15:29:48Z"],["dc.date.available","2022-02-21T15:29:48Z"],["dc.date.issued","2020"],["dc.description.abstract","Chromatin remodeling plays important roles in gene regulation during development, differentiation and in disease. The chromatin remodeling enzyme CHD4 is a component of the NuRD and ChAHP complexes that are involved in gene repression. Here, we report the cryo-electron microscopy (cryo-EM) structure of Homo sapiens CHD4 engaged with a nucleosome core particle in the presence of the non-hydrolysable ATP analogue AMP-PNP at an overall resolution of 3.1 Å. The ATPase motor of CHD4 binds and distorts nucleosomal DNA at superhelical location (SHL) +2, supporting the 'twist defect' model of chromatin remodeling. CHD4 does not induce unwrapping of terminal DNA, in contrast to its homologue Chd1, which functions in gene activation. Our structure also maps CHD4 mutations that are associated with human cancer or the intellectual disability disorder Sifrim-Hitz-Weiss syndrome."],["dc.identifier.doi","10.7554/eLife.56178"],["dc.identifier.pmid","32543371"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/100154"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/173"],["dc.language.iso","en"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","2050-084X"],["dc.relation.workinggroup","RG Cramer"],["dc.rights","CC BY 4.0"],["dc.title","Nucleosome-CHD4 chromatin remodeler structure maps human disease mutations"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]