Project B03

Project leaders:  Sergio Acebrón and Holger Bastians

The roles of Wnt signaling in genome stability

Our work demonstrated that autocrine Wnt signaling is required to maintain genome stability. Moreover, specific Wnts including Wnt10b play a key role in the regulation of DNA replication and mitosis. In addition, particular Wnt targets including the mitotic kinesin KIF2A directly regulate mitotic chromosome segregation. Based on this, we will explore how specific Wnt signals ensure genomic stability and we will investigate the biological significance of Wnt-dependent genome stability in self-renewing embryonic stem cells and in mouse embryonic development in vivo.

Die Rolle des Wnt-Signalwegs bei der Genomstabilität

Unsere bisherigen Arbeiten zeigen, dass der autokrine Wnt-Signalweg für das Erhalten der Genomstabilität essentiell ist. Außerdem konnten wir demonstrieren, dass spezifische Wnt-Liganden wie Wnt10b eine wichtige Rolle bei der Regulation der DNA-Replikation und Mitose spielen und dass spezifische Wnt-Zielproteine wie das Kinesin KIF2A direkt die mitotische Chromosomen-Segregation regulieren. Basierend auf diesen Ergebnissen werden wir untersuchen, wie spezifische Wnt-Signale Genomstabilität kontrollieren. Außerdem werden wir die Bedeutung der Wnt-abhängigen Genomstabilität in embryonalen Stammzellen und im der embryonalen Mausentwicklung in vivo analysieren.

Project-related publications

  • Bufe, A., A. García del Arco, M.I. Hennecke, A. de Jaime-Soguero, M. Ostermaier, Y.C. Lin, A. Ciprianidis, U. Engel, P. Beli, H. Bastians and S.P. Acebrón‡. 2020. Wnt signaling recruits KIF2A to the spindle to ensure chromosome congression and alignment during mitosis. PNAS. 118(34):e2108145118. PMID: 34417301
  • Giebel, N., A. de Jaime-Soguero, A. García del Arco, J.J.M. Landry, M. Tietje, L. Villacorta, V. Benes, V. Fernández-Saizand S.P. Acebrón . 2020. USP42 protects ZNRF3/RNF43 from R-spondin-dependent clearance and inhibits Wnt signalling. EMBO Reports 5;22(5):e51415. PMID: 33786993
  • Lin, YC., A. Haas, A. Bufe, S. Parbin, M. Hennecke, O. Voloshanenko, J. Gross, M. Boutros, S.P. Acebrón, and H. Bastians. 2020. Wnt10b-GSK3β-dependent Wnt/STOP signaling prevents aneuploidy in human somatic cells. Life Science Alliance. 4(1):e202000855. PMID: 33257473
  • Schmidt, AK., K. Pudelko, J.E. Boekenkamp, K. Berger, M. Kschischo, and H. Bastians. 2020. The p53/p73 - p21CIP1 tumor suppressor axis guards against chromosomal instability by restraining CDK1 in human cancer cells. Oncogene. Published online ahead of print. PMID: 33168930.
  • Bohly, N., M. Kistner, and H. Bastians. 2019. Mild replication stress causes aneuploidy by deregulating microtubule dynamics in mitosis. Cell Cycle. 18:2770-2783. PMID: 31448675.
  • Berger, B.S.*, S.P. Acebrón#,*, J. Herbst, S. Koch and C. Niehrs. 2017. Parkinson associated receptor GPR37 is an ER chaperone for LRP6. EMBO Rep. 18(5):712-725. PMID: 28341812
  • Koch, S.*, S.P. Acebrón*, J. Herbst, G. Hatiboglu, and C. Niehrs. 2015. Post-transcriptional Wnt Signaling Governs Epididymal Sperm Maturation. Cell. 163:1225-1236. PMID: 26590424
  • Huang, Y.L., Z. Anvarian, G. Doderlein, S.P. Acebrón#, and C. Niehrs. 2015. Maternal Wnt/STOP signaling promotes cell division during early Xenopus embryogenesis. Proc Natl Acad Sci U S A. 112:5732-5737. PMID: 25901317
  • Stolz, A., K. Neufeld, N. Ertych, and H. Bastians. 2015. Wnt-mediated protein stabilization ensures proper mitotic microtubule assembly and chromosome segregation. EMBO Rep. 16:490-499. PMID: 25656539.
  • Acebrón, S.P.#, E. Karaulanov, B.S. Berger, Y.L. Huang, and C. Niehrs. 2014. Mitotic wnt signaling promotes protein stabilization and regulates cell size. Mol Cell. 54:663-674. PMID: 24837680
  • Ertych, N., A. Stolz, A. Stenzinger, W. Weichert, S. Kaulfuss, P. Burfeind, A. Aigner, L. Wordeman, and H. Bastians. 2014. Increased microtubule assembly rates influence chromosomal instability in colorectal cancer cells. Nature Cell Biol. 16:779-791. PMID: 24976383.
    (* equal contribution, # Joint corresponding authorship)