Bastians, Holger

[["dc.bibliographiccitation.firstpage","492"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Nature Cell Biology"],["dc.bibliographiccitation.lastpage","499"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Stolz, Ailine"],["dc.contributor.author","Ertych, Norman"],["dc.contributor.author","Kienitz, Anne"],["dc.contributor.author","Vogel, Celia"],["dc.contributor.author","Schneider, Verena"],["dc.contributor.author","Fritz, Barbara"],["dc.contributor.author","Jacob, Ralf"],["dc.contributor.author","Dittmar, Gunnar"],["dc.contributor.author","Weichert, Wilko"],["dc.contributor.author","Petersen, Iver"],["dc.contributor.author","Bastians, Holger"],["dc.date.accessioned","2019-07-09T11:52:59Z"],["dc.date.available","2019-07-09T11:52:59Z"],["dc.date.issued","2010"],["dc.description.abstract","Chromosomal instability (CIN) is a major hallmark of human cancer and might contribute to tumorigenesis1. Genes required for the normal progression of mitosis represent potential CIN genes and, as such, are important tumour suppressors. The Chk2 kinase and its downstream targets p53 and Brca1 are tumour suppressors that have been functionally linked to the DNA damage response pathway2. Here, we report a function of Chk2, independent of p53 and DNA damage, that is required for proper progression of mitosis, and for the maintenance of chromosomal stability in human somatic cells. Depletion of Chk2 or abrogation of its kinase activity causes abnormal mitotic spindle assembly associated with a delay in mitosis, which promotes the generation of lagging chromosomes, chromosome missegregation and CIN, while still allowing survival and growth. Furthermore, we have identified Brca1 as a mitotic target of the Chk2 kinase in the absence of DNA damage. Accordingly, loss of BRCA1 or its Chk2-mediated phosphorylation leads to spindle formation defects and CIN. Thus, the CHK2–BRCA1 tumour suppressor pathway is required for chromosomal stability, which might contribute to their tumour suppressor function."],["dc.identifier.doi","10.1038/ncb2051"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6282"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60314"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","The CHK2–BRCA1 tumour suppressor pathway ensures chromosomal stability in human somatic cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e201900499"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Life Science Alliance"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Schukken, Klaske M"],["dc.contributor.author","Lin, Yu-Chih"],["dc.contributor.author","Bakker, Petra L"],["dc.contributor.author","Schubert, Michael"],["dc.contributor.author","Preuss, Stephanie F"],["dc.contributor.author","Simon, Judith E"],["dc.contributor.author","van den Bos, Hilda"],["dc.contributor.author","Storchova, Zuzana"],["dc.contributor.author","Colomé-Tatché, Maria"],["dc.contributor.author","Bastians, Holger"],["dc.contributor.author","Spierings, Diana CJ"],["dc.contributor.author","Foijer, Floris"],["dc.date.accessioned","2021-04-14T08:27:22Z"],["dc.date.available","2021-04-14T08:27:22Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.26508/lsa.201900499"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17230"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82264"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","2575-1077"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Altering microtubule dynamics is synergistically toxic with spindle assembly checkpoint inhibition"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","47061"],["dc.bibliographiccitation.issue","30"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","47081"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Schrader, Alexandra"],["dc.contributor.author","Meyer, Katharina"],["dc.contributor.author","Walther, Neele"],["dc.contributor.author","Stolz, Ailine"],["dc.contributor.author","Feist, Maren"],["dc.contributor.author","Hand, Elisabeth"],["dc.contributor.author","von Bonin, Frederike"],["dc.contributor.author","Evers, Maurits"],["dc.contributor.author","Kohler, Christian W."],["dc.contributor.author","Shirneshan, Katayoon"],["dc.contributor.author","Vockerodt, Martina"],["dc.contributor.author","Klapper, Wolfram"],["dc.contributor.author","Szczepanowski, Monika"],["dc.contributor.author","Murray, Paul G."],["dc.contributor.author","Bastians, Holger"],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Spang, Rainer"],["dc.contributor.author","Kube, Dieter"],["dc.date.accessioned","2018-11-07T10:11:28Z"],["dc.date.available","2018-11-07T10:11:28Z"],["dc.date.issued","2016"],["dc.description.abstract","To discover new regulatory pathways in B lymphoma cells, we performed a combined analysis of experimental, clinical and global gene expression data. We identified a specific cluster of genes that was coherently expressed in primary lymphoma samples and suppressed by activation of the B cell receptor (BCR) through aIgM treatment of lymphoma cells in vitro. This gene cluster, which we called BCR. 1, includes numerous cell cycle regulators. A reduced expression of BCR. 1 genes after BCR activation was observed in different cell lines and also in CD10(+) germinal center B cells. We found that BCR activation led to a delayed entry to and progression of mitosis and defects in metaphase. Cytogenetic changes were detected upon long-term aIgM treatment. Furthermore, an inverse correlation of BCR. 1 genes with c-Myc co-regulated genes in distinct groups of lymphoma patients was observed. Finally, we showed that the BCR. 1 index discriminates activated B cell-like and germinal centre B cell-like diffuse large B cell lymphoma supporting the functional relevance of this new regulatory circuit and the power of guided clustering for biomarker discovery."],["dc.identifier.doi","10.18632/oncotarget.9219"],["dc.identifier.isi","000385413000020"],["dc.identifier.pmid","27166259"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14137"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40052"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Impact Journals Llc"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Identification of a new gene regulatory circuit involving B cell receptor activated signaling using a combined analysis of experimental, clinical and global gene expression data"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","4"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Clinical Epigenetics"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Raul, Sanjay K"],["dc.contributor.author","Henck, Jana M"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Kosinsky, Robyn L"],["dc.contributor.author","Übelmesser, Nadine"],["dc.contributor.author","Mansour, Wael Y"],["dc.contributor.author","Eggert, Jessica"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Najafova, Zeynab"],["dc.contributor.author","Bastians, Holger"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Johnsen, Steven A"],["dc.date.accessioned","2019-07-09T11:49:49Z"],["dc.date.available","2019-07-09T11:49:49Z"],["dc.date.issued","2019"],["dc.description.abstract","Abstract Background Disruptor of telomeric silencing 1-like (DOT1L) is a non-SET domain containing methyltransferase known to catalyze mono-, di-, and tri-methylation of histone 3 on lysine 79 (H3K79me). DOT1L-mediated H3K79me has been implicated in chromatin-associated functions including gene transcription, heterochromatin formation, and DNA repair. Recent studies have uncovered a role for DOT1L in the initiation and progression of leukemia and other solid tumors. The development and availability of small molecule inhibitors of DOT1L may provide new and unique therapeutic options for certain types or subgroups of cancer. Methods In this study, we examined the role of DOT1L in DNA double-strand break (DSB) response and repair by depleting DOT1L using siRNA or inhibiting its methyltransferase activity using small molecule inhibitors in colorectal cancer cells. Cells were treated with different agents to induce DNA damage in DOT1L-depleted or -inhibited cells and analyzed for DNA repair efficiency and survival. Further, rectal cancer patient samples were analyzed for H3K79me3 levels in order to determine whether it may serve as a potential marker for personalized therapy. Results Our results indicate that DOT1L is required for a proper DNA damage response following DNA double-strand breaks by regulating the phosphorylation of the variant histone H2AX (γH2AX) and repair via homologous recombination (HR). Importantly, we show that small molecule inhibitors of DOT1L combined with chemotherapeutic agents that are used to treat colorectal cancers show additive effects. Furthermore, examination of H3K79me3 levels in rectal cancer patients demonstrates that lower levels correlate with a poorer prognosis. Conclusions In this study, we conclude that DOT1L plays an important role in an early DNA damage response and repair of DNA double-strand breaks via the HR pathway. Moreover, DOT1L inhibition leads to increased sensitivity to chemotherapeutic agents and PARP inhibition, which further highlights its potential clinical utility. Our results further suggest that H3K79me3 can be useful as a predictive and or prognostic marker for rectal cancer patients."],["dc.identifier.doi","10.1186/s13148-018-0601-1"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15787"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59638"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","BioMed Central"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The histone methyltransferase DOT1L is required for proper DNA damage response, DNA repair, and modulates chemotherapy responsiveness"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]