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","2398"],["dc.bibliographiccitation.issue","18"],["dc.bibliographiccitation.journal","Oncogene"],["dc.bibliographiccitation.lastpage","2406"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Lueddecke, S."],["dc.contributor.author","Ertych, Norman"],["dc.contributor.author","Stenzinger, Albrecht"],["dc.contributor.author","Weichert, Wilko"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Dyczkowski, Jerzy"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Valerius, Oliver"],["dc.contributor.author","Braus, Gerhard H."],["dc.contributor.author","Kschischo, M."],["dc.contributor.author","Bastians, Holger Dirk"],["dc.date.accessioned","2018-11-07T10:14:25Z"],["dc.date.available","2018-11-07T10:14:25Z"],["dc.date.issued","2016"],["dc.description.abstract","BRCA1 is a tumor-suppressor gene associated with, but not restricted to, breast and ovarian cancer and implicated in various biological functions. During mitosis, BRCA1 and its positive regulator Chk2 are localized at centrosomes and are required for the regulation of microtubule plus end assembly, thereby ensuring faithful mitosis and numerical chromosome stability. However, the function of BRCA1 during mitosis has not been defined mechanistically. To gain insights into the mitotic role of BRCA1 in regulating microtubule assembly, we systematically identified proteins interacting with BRCA1 during mitosis and found the centrosomal protein Cep72 as a novel BRCA1-interacting protein. CEP72 is frequently upregulated in colorectal cancer tissues and overexpression of CEP72 mirrors the consequences of BRCA1 loss during mitosis. In detail, the overexpression of CEP72 causes an increase in microtubule plus end assembly, abnormal mitotic spindle formation and the induction of chromosomal instability. Moreover, we show that high levels of Cep72 counteract Chk2 as a positive regulator of BRCA1 to ensure proper mitotic microtubule assembly. Thus, CEP72 represents a putative oncogene in colorectal cancer that might negatively regulate the mitotic function of BRCA1 to ensure chromosomal stability."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft; DFG"],["dc.identifier.doi","10.1038/onc.2015.290"],["dc.identifier.isi","000376165000012"],["dc.identifier.pmid","26300001"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40613"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1476-5594"],["dc.relation.issn","0950-9232"],["dc.title","The putative oncogene CEP72 inhibits the mitotic function of BRCA1 and induces chromosomal instability"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","779"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Nature Cell Biology"],["dc.bibliographiccitation.lastpage","U274"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Ertych, Norman"],["dc.contributor.author","Stolz, Ailine"],["dc.contributor.author","Stenzinger, Albrecht"],["dc.contributor.author","Weichert, Wilko"],["dc.contributor.author","Kaulfuss, Silke"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Aigner, Achim"],["dc.contributor.author","Wordeman, Linda"],["dc.contributor.author","Bastians, Holger"],["dc.date.accessioned","2018-11-07T09:37:16Z"],["dc.date.available","2018-11-07T09:37:16Z"],["dc.date.issued","2014"],["dc.description.abstract","Chromosomal instability (CIN) is defined as the perpetual missegregation of whole chromosomes during mitosis and represents a hallmark of human cancer. However, the mechanisms influencing CIN and its consequences on tumour growth are largely unknown. We identified an increase in microtubule plus-end assembly rates as a mechanism influencing CIN in colorectal cancer cells. This phenotype is induced by overexpression of the oncogene AURKA or by loss of the tumour suppressor gene CHK2, a genetic constitution found in 73% of human colorectal cancers. Increased microtubule assembly rates are associated with transient abnormalities in mitotic spindle geometry promoting the generation of lagging chromosomes and influencing CIN. Reconstitution of proper microtubule assembly rates by chemical or genetic means suppresses CIN and thereby, unexpectedly, accelerates tumour growth in vitro and in vivo. Thus, we identify a fundamental mechanism influencing CIN in cancer cells and reveal its adverse consequence on tumour growth."],["dc.identifier.doi","10.1038/ncb2994"],["dc.identifier.isi","000339904900010"],["dc.identifier.pmid","24976383"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32803"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1476-4679"],["dc.relation.issn","1465-7392"],["dc.title","Increased microtubule assembly rates influence chromosomal instability in colorectal cancer cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]