Gaedcke, Jochen

[["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","12574"],["dc.bibliographiccitation.issue","14"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","12586"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Srinivas, Upadhyayula Sai"],["dc.contributor.author","Dyczkowski, Jerzy"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Mansour, Wael Y."],["dc.contributor.author","Borgmann, Kerstin"],["dc.contributor.author","Dobbelstein, Matthias"],["dc.date.accessioned","2019-07-09T11:42:37Z"],["dc.date.available","2019-07-09T11:42:37Z"],["dc.date.issued","2015-05-20"],["dc.description.abstract","Malignant tumors of the rectum are treated by neoadjuvant radiochemotherapy. This involves a combination of 5-fluorouracil (5-FU) and double stranded DNA-break (DSB)-inducing radiotherapy. Here we explored how 5-FU cooperates with DSB-induction to achieve sustainable DNA damage in colorectal cancer (CRC) cells. After DSB induction by neocarzinostatin, phosphorylated histone 2AX (γ-H2AX) rapidly accumulated but then largely vanished within a few hours. In contrast, when CRC cells were pre-treated with 5-FU, gammaH2AX remained for at least 24 hours. GFP-reporter assays revealed that 5-FU decreases the efficiency of homologous recombination (HR) repair. However, 5-FU did not prevent the initial steps of HR repair, such as the accumulation of RPA and Rad51 at nuclear foci. Thus, we propose that 5-FU interferes with the continuation of HR repair, e. g. the synthesis of new DNA strands. Two key mediators of HR, Rad51 and BRCA2, were found upregulated in CRC biopsies as compared to normal mucosa. Inhibition of HR by targeting Rad51 enhanced DNA damage upon DSB-inducing treatment, outlining an alternative way of enhancing therapeutic efficacy. Taken together, our results strongly suggest that interfering with HR represents a key mechanism to enhance the efficacy when treating CRC with DNA-damaging therapy."],["dc.identifier.doi","10.18632/oncotarget.3728"],["dc.identifier.fs","612071"],["dc.identifier.pmid","25909291"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13608"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58708"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.subject.mesh","Antineoplastic Agents"],["dc.subject.mesh","Cell Line, Tumor"],["dc.subject.mesh","Chemoradiotherapy"],["dc.subject.mesh","Colorectal Neoplasms"],["dc.subject.mesh","DNA Breaks, Double-Stranded"],["dc.subject.mesh","Flow Cytometry"],["dc.subject.mesh","Fluorouracil"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Immunoblotting"],["dc.subject.mesh","Microscopy, Confocal"],["dc.subject.mesh","Microscopy, Fluorescence"],["dc.subject.mesh","Oligonucleotide Array Sequence Analysis"],["dc.subject.mesh","Recombinational DNA Repair"],["dc.subject.mesh","Reverse Transcriptase Polymerase Chain Reaction"],["dc.title","5-Fluorouracil sensitizes colorectal tumor cells towards double stranded DNA breaks by interfering with homologous recombination repair."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]