Bastians, Holger

[["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","95"],["dc.bibliographiccitation.lastpage","113"],["dc.contributor.author","Bastians, Holger"],["dc.contributor.editor","Ghadimi, B. Michael"],["dc.contributor.editor","Ried, Thomas"],["dc.date.accessioned","2021-06-02T10:44:29Z"],["dc.date.available","2021-06-02T10:44:29Z"],["dc.date.issued","2015"],["dc.identifier.doi","10.1007/978-3-319-20291-4_5"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87058"],["dc.notes.intern","DOI-Import GROB-425"],["dc.publisher","Springer International Publishing"],["dc.publisher.place","Cham"],["dc.relation.eisbn","978-3-319-20291-4"],["dc.relation.isbn","978-3-319-20290-7"],["dc.relation.ispartof","Chromosomal Instability in Cancer Cells"],["dc.title","Causes of Chromosomal Instability"],["dc.type","book_chapter"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","67"],["dc.bibliographiccitation.lastpage","75"],["dc.bibliographiccitation.seriesnr","1787"],["dc.contributor.author","Glaubke, Elina"],["dc.contributor.author","Bastians, Holger"],["dc.contributor.editor","Wagner, Bridget"],["dc.date.accessioned","2021-06-02T10:44:26Z"],["dc.date.available","2021-06-02T10:44:26Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1007/978-1-4939-7847-2_5"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87036"],["dc.notes.intern","DOI-Import GROB-425"],["dc.publisher","Springer New York"],["dc.publisher.place","New York, NY"],["dc.relation.crisseries","Methods in Molecular Biology"],["dc.relation.eisbn","978-1-4939-7847-2"],["dc.relation.isbn","978-1-4939-7846-5"],["dc.relation.ispartof","Methods in Molecular Biology"],["dc.relation.ispartof","Phenotypic Screening"],["dc.relation.ispartofseries","Methods in Molecular Biology; 1787"],["dc.title","A Cell-Based Assay for Mitotic Spindle Orientation"],["dc.type","book_chapter"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","401"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Clinical Cancer Research"],["dc.bibliographiccitation.lastpage","405"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Stolz, Ailine"],["dc.contributor.author","Ertych, Norman"],["dc.contributor.author","Bastians, Holger"],["dc.date.accessioned","2018-11-07T08:59:45Z"],["dc.date.available","2018-11-07T08:59:45Z"],["dc.date.issued","2011"],["dc.description.abstract","CHK2 is a multiorgan tumor susceptibility gene that encodes for a serine/threonine protein kinase involved in the response to cellular DNA damage. After ATM-mediated phosphorylation, the activated Chk2 kinase can act as a signal transducer and phosphorylate a variety of substrates, including the Cdc25 phosphatases, p53, PML, E2F-1, and Brca1, which has been associated with halting the cell cycle, the initiation of DNA repair, and the induction of apoptosis after DNA damage. In addition, recent work has revealed another, DNA-damage-independent function of Chk2 during mitosis that is required for proper mitotic spindle assembly and maintenance of chromosomal stability. This novel role involves a mitotic phosphorylation of the tumor suppressor Brca1 by the Chk2 kinase. On the basis of its role during DNA damage response, Chk2 has been suggested as an anticancer therapy target, but given its recently discovered new function and its role as a tumor suppressor, it is questionable whether inhibition of Chk2 is indeed beneficial for anticancer treatment. However, investigators may be able to exploit the loss of CHK2 in human tumors to develop novel therapies based on synthetic lethal interactions. Clin Cancer Res; 17(3); 401-5. (C) 2010 AACR."],["dc.identifier.doi","10.1158/1078-0432.CCR-10-1215"],["dc.identifier.isi","000286873400003"],["dc.identifier.pmid","21088254"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23979"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","1078-0432"],["dc.title","Tumor Suppressor CHK2: Regulator of DNA Damage Response and Mediator of Chromosomal Stability"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e960768"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Molecular & Cellular Oncology"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Stolz, Ailine"],["dc.contributor.author","Ertych, Norman"],["dc.contributor.author","Bastians, Holger"],["dc.date.accessioned","2021-06-01T10:48:54Z"],["dc.date.available","2021-06-01T10:48:54Z"],["dc.date.issued","2014"],["dc.identifier.doi","10.4161/23723548.2014.960768"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86093"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.eissn","2372-3556"],["dc.title","Microtubule plus tips: A dynamic route to chromosomal instability"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e202000855"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Life Science Alliance"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Lin, Yu-Chih"],["dc.contributor.author","Haas, Alexander"],["dc.contributor.author","Bufe, Anja"],["dc.contributor.author","Parbin, Sabnam"],["dc.contributor.author","Hennecke, Magdalena"],["dc.contributor.author","Voloshanenko, Oksana"],["dc.contributor.author","Gross, Julia"],["dc.contributor.author","Boutros, Michael"],["dc.contributor.author","Acebron, Sergio P"],["dc.contributor.author","Bastians, Holger"],["dc.date.accessioned","2021-04-14T08:29:53Z"],["dc.date.available","2021-04-14T08:29:53Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.26508/lsa.202000855"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83017"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","2575-1077"],["dc.title","Wnt10b-GSK3β–dependent Wnt/STOP signaling prevents aneuploidy in human somatic cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","490"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","EMBO Reports"],["dc.bibliographiccitation.lastpage","499"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Stolz, Ailine"],["dc.contributor.author","Neufeld, Kim"],["dc.contributor.author","Ertych, Norman"],["dc.contributor.author","Bastians, Holger"],["dc.date.accessioned","2021-06-01T10:48:25Z"],["dc.date.available","2021-06-01T10:48:25Z"],["dc.date.issued","2015"],["dc.description.abstract","Wnt signaling stimulates cell proliferation by promoting the G1/S transition of the cell cycle through beta-catenin/TCF4-mediated gene transcription. However, Wnt signaling peaks in mitosis and contributes to the stabilization of proteins other than beta-catenin, a pathway recently introduced as Wnt-dependent stabilization of proteins (Wnt/STOP). Here, we show that Wnt/STOP regulated by basal Wnt signaling during a normal cell cycle is required for proper spindle microtubule assembly and for faithful chromosome segregation during mitosis. Consequently, inhibition of basal Wnt signaling results in increased microtubule assembly rates, abnormal mitotic spindle formation and the induction of aneuploidy in human somatic cells."],["dc.identifier.doi","10.15252/embr.201439410"],["dc.identifier.isi","352167500012"],["dc.identifier.pmid","25656539"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85930"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.eissn","1469-3178"],["dc.relation.issn","1469-221X"],["dc.title","Wnt‐mediated protein stabilization ensures proper mitotic microtubule assembly and chromosome segregation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2770"],["dc.bibliographiccitation.issue","20"],["dc.bibliographiccitation.journal","Cell Cycle"],["dc.bibliographiccitation.lastpage","2783"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Böhly, Nicolas"],["dc.contributor.author","Kistner, Magdalena"],["dc.contributor.author","Bastians, Holger"],["dc.date.accessioned","2020-12-10T18:15:14Z"],["dc.date.available","2020-12-10T18:15:14Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1080/15384101.2019.1658477"],["dc.identifier.eissn","1551-4005"],["dc.identifier.issn","1538-4101"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/74789"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Mild replication stress causes aneuploidy by deregulating microtubule dynamics in mitosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1817"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"],["dc.bibliographiccitation.lastpage","1822"],["dc.bibliographiccitation.volume","113"],["dc.contributor.author","Ertych, Norman"],["dc.contributor.author","Stolz, Ailine"],["dc.contributor.author","Valerius, Oliver"],["dc.contributor.author","Braus, Gerhard H."],["dc.contributor.author","Bastians, Holger"],["dc.date.accessioned","2018-11-07T10:18:11Z"],["dc.date.available","2018-11-07T10:18:11Z"],["dc.date.issued","2016"],["dc.description.abstract","BRCA1 (breast cancer type 1 susceptibility protein) is a multifunctional tumor suppressor involved in DNA damage response, DNA repair, chromatin regulation, and mitotic chromosome segregation. Although the nuclear functions of BRCA1 have been investigated in detail, its role during mitosis is little understood. It is clear, however, that loss of BRCA1 in human cancer cells leads to chromosomal instability (CIN), which is defined as a perpetual gain or loss of whole chromosomes during mitosis. Moreover, our recent work has revealed that the mitotic function of BRCA1 depends on its phosphorylation by the tumor-suppressor kinase Chk2 (checkpoint kinase 2) and that this regulation is required to ensure normal microtubule plus end assembly rates within mitotic spindles. Intriguingly, loss of the positive regulation of BRCA1 leads to increased oncogenic Aurora-A activity, which acts as a mediator for abnormal mitotic microtubule assembly resulting in chromosome missegregation and CIN. However, how the CHK2-BRCA1 tumor suppressor axis restrains oncogenic Aurora-A during mitosis to ensure karyotype stability remained an open question. Here we uncover a dual molecular mechanism by which the CHK2-BRCA1 axis restrains oncogenic Aurora-A activity during mitosis and identify BRCA1 itself as a target for Aurora-A relevant for CIN. In fact, Chk2-mediated phosphorylation of BRCA1 is required to recruit the PP6C-SAPS3 phosphatase, which acts as a T-loop phosphatase inhibiting Aurora-A bound to BRCA1. Consequently, loss of CHK2 or PP6C-SAPS3 promotes Aurora-A activity associated with BRCA1 in mitosis. Aurora-A, in turn, then phosphorylates BRCA1 itself, thereby inhibiting the mitotic function of BRCA1 and promoting mitotic microtubule assembly, chromosome missegregation, and CIN."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft (DFG); DFG [KFO179]"],["dc.identifier.doi","10.1073/pnas.1525129113"],["dc.identifier.isi","000370220000047"],["dc.identifier.pmid","26831064"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41385"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","CHK2-BRCA1 tumor-suppressor axis restrains oncogenic Aurora-A kinase to ensure proper mitotic microtubule assembly"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]