Kramer, Daniela

[["dc.bibliographiccitation.firstpage","780"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cell Death and Differentiation"],["dc.bibliographiccitation.lastpage","780"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Kramer, Daniela"],["dc.contributor.author","Stark, Nadine"],["dc.contributor.author","Schulz-Heddergott, Ramona"],["dc.contributor.author","Erytch, Norman"],["dc.contributor.author","Edmunds, Shelley"],["dc.contributor.author","Roßmann, Laura"],["dc.contributor.author","Bastians, Holger"],["dc.contributor.author","Concin, Nicole"],["dc.contributor.author","Moll, Ute M."],["dc.contributor.author","Dobbelstein, Matthias"],["dc.date.accessioned","2020-12-10T18:09:42Z"],["dc.date.available","2020-12-10T18:09:42Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1038/s41418-018-0190-8"],["dc.identifier.eissn","1476-5403"],["dc.identifier.issn","1350-9047"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73731"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation.iserratumof","/handle/2/43281"],["dc.title","Correction: Strong antitumor synergy between DNA crosslinking and HSP90 inhibition causes massive premitotic DNA fragmentation in ovarian cancer cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","erratum_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","300"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Cell Death and Differentiation"],["dc.bibliographiccitation.lastpage","316"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Kramer, Daniela"],["dc.contributor.author","Stark, Nadine"],["dc.contributor.author","Schulz-Heddergott, Ramona"],["dc.contributor.author","Erytch, Norman"],["dc.contributor.author","Edmunds, Shelley"],["dc.contributor.author","Rossmann, Laura"],["dc.contributor.author","Bastians, Holger"],["dc.contributor.author","Concin, Nicole"],["dc.contributor.author","Moll, Ute M."],["dc.contributor.author","Dobbelstein, Matthias"],["dc.date.accessioned","2018-11-07T10:27:41Z"],["dc.date.available","2018-11-07T10:27:41Z"],["dc.date.issued","2017"],["dc.description.abstract","All current regimens for treating ovarian cancer center around carboplatin as standard first line. The HSP90 inhibitor ganetespib is currently being assessed in advanced clinical oncology trials. Thus, we tested the combined effects of ganetespib and carboplatin on a panel of 15 human ovarian cancer lines. Strikingly, the two drugs strongly synergized in cytotoxicity in tumor cells lacking wild-type p53. Mechanistically, ganetespib and carboplatin in combination, but not individually, induced persistent DNA damage causing massive global chromosome fragmentation. Live-cell microscopy revealed chromosome fragmentation occurring to a dramatic degree when cells condensed their chromatin in preparation for mitosis, followed by cell death in mitosis or upon aberrant exit from mitosis. HSP90 inhibition caused the rapid decay of key components of the Fanconi anemia pathway required for repair of carboplatin-induced interstrand crosslinks (ICLs), as well as of cell cycle checkpoint mediators. Overexpressing FancA rescued the DNA damage induced by the drug combination, indicating that FancA is indeed a key client of Hsp90 that enables cancer cell survival in the presence of ICLs. Conversely, depletion of nuclease DNA2 prevented chromosomal fragmentation, pointing to an imbalance of defective repair in the face of uncontrolled nuclease activity as mechanistic basis for the observed premitotic DNA fragmentation. Importantly, the drug combination induced robust antitumor activity in xenograft models, again accompanied with depletion of FancA. In sum, our findings indicate that ganetespib strongly potentiates the antitumor efficacy of carboplatin by causing combined inhibition of DNA repair and cell cycle control mechanisms, thus triggering global chromosome disruption, aberrant mitosis and cell death."],["dc.identifier.doi","10.1038/cdd.2016.124"],["dc.identifier.isi","000395789500012"],["dc.identifier.pmid","27834954"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43281"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.haserratum","/handle/2/73731"],["dc.relation.issn","1476-5403"],["dc.relation.issn","1350-9047"],["dc.title","Strong antitumor synergy between DNA crosslinking and HSP90 inhibition causes massive premitotic DNA fragmentation in ovarian cancer cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","68"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Cell"],["dc.bibliographiccitation.lastpage","83"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Wienken, Magdalena"],["dc.contributor.author","Dickmanns, Antje"],["dc.contributor.author","Nemajerova, Alice"],["dc.contributor.author","Kramer, Daniela"],["dc.contributor.author","Najafova, Zeynab"],["dc.contributor.author","Weiss, Miriam"],["dc.contributor.author","Karpiuk, Oleksandra"],["dc.contributor.author","Kassem, Moustapha"],["dc.contributor.author","Zhang, Y."],["dc.contributor.author","Lozano, Guillermina"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Moll, Ute M."],["dc.contributor.author","Zhang, X."],["dc.contributor.author","Dobbelstein, Matthias"],["dc.date.accessioned","2018-11-07T10:19:27Z"],["dc.date.available","2018-11-07T10:19:27Z"],["dc.date.issued","2016"],["dc.description.abstract","The MDM2 oncoprotein ubiquitinates and antagonizes p53 but may also carry out p53-independent functions. Here we report that MDM2 is required for the efficient generation of induced pluripotent stem cells (iPSCs) from murine embryonic fibroblasts, in the absence of p53. Similarly, MDM2 depletion in the context of p53 deficiency also promoted the differentiation of human mesenchymal stem cells and diminished clonogenic survival of cancer cells. Most of the MDM2-controlled genes also responded to the inactivation of the Polycomb Repressor Complex 2 (PRC2) and its catalytic component EZH2. MDM2 physically associated with EZH2 on chromatin, enhancing the trimethylation of histone 3 at lysine 27 and the ubiquitination of histone 2A at lysine 119 (H2AK119) at its target genes. Removing MDM2 simultaneously with the H2AK119 E3 ligase Ring1B/RNF2 further induced these genes and synthetically arrested cell proliferation. In conclusion, MDM2 supports the Polycomb-mediated repression of lineage-specific genes, independent of p53."],["dc.identifier.doi","10.1016/j.molcel.2015.12.008"],["dc.identifier.isi","000372324500007"],["dc.identifier.pmid","26748827"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41663"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cell Press"],["dc.relation.issn","1097-4164"],["dc.relation.issn","1097-2765"],["dc.title","MDM2 Associates with Polycomb Repressor Complex 2 and Enhances Stemness-Promoting Chromatin Modifications Independent of p53"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1300"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Genes & Development"],["dc.bibliographiccitation.lastpage","1312"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Nemajerova, Alice"],["dc.contributor.author","Kramer, Daniela"],["dc.contributor.author","Siller, Saul S."],["dc.contributor.author","Herr, Christian"],["dc.contributor.author","Shomroni, Orr"],["dc.contributor.author","Pena, Tonatiuh"],["dc.contributor.author","Suazo, Cristina Gallinas"],["dc.contributor.author","Glaser, Katharina"],["dc.contributor.author","Wildung, Merit"],["dc.contributor.author","Steffen, Henrik"],["dc.contributor.author","Sriraman, Anusha"],["dc.contributor.author","Oberle, Fabian"],["dc.contributor.author","Wienken, Magdalena"],["dc.contributor.author","Hennion, Magali"],["dc.contributor.author","Vidal, Ramon"],["dc.contributor.author","Royen, Bettina"],["dc.contributor.author","Alevra, Mihai"],["dc.contributor.author","Schild, Detlev"],["dc.contributor.author","Bals, Robert"],["dc.contributor.author","Doenitz, Juergen"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Takemaru, Ken-Ichi"],["dc.contributor.author","Moll, Ute M."],["dc.contributor.author","Lize, Muriel"],["dc.date.accessioned","2018-11-07T10:13:24Z"],["dc.date.available","2018-11-07T10:13:24Z"],["dc.date.issued","2016"],["dc.description.abstract","Motile multiciliated cells (MCCs) have critical roles in respiratory health and disease and are essential for cleaning inhaled pollutants and pathogens from airways. Despite their significance for human disease, the transcriptional control that governs multiciliogenesis remains poorly understood. Here we identify TP73, a p53 homolog, as governing the program for airway multiciliogenesis. Mice with TP73 deficiency suffer from chronic respiratory tract infections due to profound defects in ciliogenesis and complete loss of mucociliary clearance. Organotypic airway cultures pinpoint TAp73 as necessary and sufficient for basal body docking, axonemal extension, and motility during the differentiation of MCC progenitors. Mechanistically, cross-species genomic analyses and complete ciliary rescue of knockout MCCs identify TAp73 as the conserved central transcriptional integrator of multiciliogenesis. TAp73 directly activates the key regulators FoxJ1, Rfx2, Rfx3, and miR34bc plus nearly 50 structural and functional ciliary genes, some of which are associated with human ciliopathies. Our results position TAp73 as a novel central regulator of MCC differentiation."],["dc.identifier.doi","10.1101/gad.279836.116"],["dc.identifier.isi","000378084000006"],["dc.identifier.pmid","27257214"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40428"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cold Spring Harbor Lab Press, Publications Dept"],["dc.relation.issn","1549-5477"],["dc.relation.issn","0890-9369"],["dc.title","TAp73 is a central transcriptional regulator of airway multiciliogenesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1173"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","The Journal of Cell Biology"],["dc.bibliographiccitation.lastpage","1190"],["dc.bibliographiccitation.volume","204"],["dc.contributor.author","Holembowski, Lena"],["dc.contributor.author","Kramer, Daniela"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Sordella, Raffaella"],["dc.contributor.author","Nemajerova, Alice"],["dc.contributor.author","Dobbelstein, Matthias"],["dc.contributor.author","Moll, Ute M."],["dc.date.accessioned","2018-11-07T09:42:22Z"],["dc.date.available","2018-11-07T09:42:22Z"],["dc.date.issued","2014"],["dc.description.abstract","A core evolutionary function of the p53 family is to protect the genomic integrity of gametes. However, the role of p73 in the male germ line is unknown. Here, we reveal that TAp73 unexpectedly functions as an adhesion and maturation factor of the seminiferous epithelium orchestrating spermiogenesis. TAp73 knockout (TAp73KO) and p73KO mice, but not. Np73KO mice, display a \"near-empty seminiferous tubule\" phenotype due to massive premature loss of immature germ cells. The cellular basis of this phenotype is defective cell-cell adhesions of developing germ cells to Sertoli nurse cells, with likely secondary degeneration of Sertoli cells, including the blood-testis barrier, which leads to disruption of the adhesive integrity and maturation of the germ epithelium. At the molecular level, TAp73, which is produced in germ cells, controls a coordinated transcriptional program of adhesion-and migrationrelated proteins including peptidase inhibitors, proteases, receptors, and integrins required for germ-Sertoli cell adhesion and dynamic junctional restructuring. Thus, we propose the testis as a unique organ with strict division of labor among all family members: p63 and p53 safeguard germ line fidelity, whereas TAp73 ensures fertility by enabling sperm maturation."],["dc.description.sponsorship","National Cancer Institute [CA93853]; Deutsche Krebshilfe [108775]"],["dc.identifier.doi","10.1083/jcb.201306066"],["dc.identifier.isi","000333903600010"],["dc.identifier.pmid","24662569"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33940"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Rockefeller Univ Press"],["dc.relation.issn","1540-8140"],["dc.relation.issn","0021-9525"],["dc.title","TAp73 is essential for germ cell adhesion and maturation in testis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]