B03

The roles of Wnt signaling in genome stability

Funding period: 2017-2025

Project B03

Project Leaders

Dr. Sergio Acebrón

Dr. Sergio P. Acebrón

Project Leader B03
Prof. Dr. Holger Bastians

Prof. Dr. Holger Bastians

Project Leader B03

Abstract

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.

Project-related Publications

Wnt signaling recruits KIF2A to the spindle to ensure chromosome congression and alignment during mitosis

Bufe A, García Del Arco A, Hennecke M, de Jaime-Soguero A, Ostermaier M, Lin YC, Ciprianidis A, Hattemer J, Engel U, Beli P, Bastians H, Acebrón SP. Proc Natl Acad Sci U S A. 2021 Aug 24; 118(34):e2108145118. doi:10.1073/pnas.2108145118. PMID: 34417301

Learn more
USP42 protects ZNRF3/RNF43 from R‐spondin‐dependent clearance and inhibits Wnt signalling

Giebel N, de Jaime-Soguero A, García Del Arco A, Landry JJM, Tietje M, Villacorta L, Benes V, Fernández-Sáiz V, Acebrón SP. EMBO Rep. 2021 Mar 30:e51415. doi: 10.15252/embr.202051415. Online ahead of print.
PMID: 33786993

Learn more
Wnt10b GSK3β dependent Wnt/STOP signaling prevents aneuploidy in human somatic cells

Lin YC, Haas A, Bufe A, Parbin S, Hennecke M, Voloshanenko O, Gross J, Boutros M, Acebron SP, Bastians H. Life Sci Alliance. 2020 Nov 30;4(1):e202000855. Print 2021 Jan.
PMID: 33257473

Learn more
The p53/p73 – p21CIP1 tumor suppressor axis guards against chromosomal instability by restraining CDK1 in human cancer cells

Schmidt AK, Pudelko K, Boekenkamp JE, Berger K, Kschischo M, Bastians H. Oncogene. 2021 Jan;40(2):436-451. doi: 10.1038/s41388-020-01524-4. Epub 2020 Nov 9. PMID: 33168930

Learn more
Mild replication stress causes aneuploidy by deregulating microtubule dynamics in mitosis

Böhly N, Kistner M, Bastians H. Cell Cycle. 2019 Oct;18(20):2770-2783. doi: 10.1080/15384101.2019.1658477. Epub 2019 Aug 25. PMID: 31448675

Learn more
A Cell-Based Assay for Mitotic Spindle Orientation

Glaubke E, Bastians H. Methods Mol Biol. 2018;1787:67-75. doi: 10.1007/978-1-4939-7847-2_5. PMID:29736710

Learn more
Parkinson associated receptor GPR37 is an ER chaperone for LRP6

Berger BS, Acebron SP, Herbst J, Koch S, Niehrs C. EMBO Rep. 2017 May;18(5):712-725. doi: 10.15252/embr.201643585. Epub 2017 Mar 24. PMID: 28341812

Learn more
Posttranscriptional Wnt signaling governs epididymal sperm maturation

Koch S, Acebron SP, Herbst J, Hatiboglu G, Niehrs C. Cell. 2015 Nov 19;163(5):1225-1236. doi: 10.1016/j.cell.2015.10.029. PMID: 26590424

Learn more
Maternal Wnt/STOP signaling promotes cell division during early Xenopus embryogenesis

Huang YL, Anvarian Z, Döderlein G, Acebron SP, Niehrs C. Proc Natl Acad Sci U S A. 2015 May 5;112(18):5732-7. doi: 10.1073/pnas.1423533112. Epub 2015 Apr 21. PMID: 25901317

Learn more
Wnt-mediated protein stabilization ensures proper mitotic microtubule assembly and chromosome segregation

Stolz A, Neufeld K, Ertych N, Bastians H. EMBO Rep. 2015 Apr;16(4):490-9. doi: 10.15252/embr.201439410. Epub 2015 Feb 5. PMID: 25656539

Learn more
Increased microtubule assembly rates influence chromosomal instability in colorectal cancer cells.

Ertych N, Stolz A, Stenzinger A, Weichert W, Kaulfuß S, Burfeind P, Aigner A, Wordeman L, Bastians H. Nat Cell Biol. 2014 Aug;16(8):779-91. doi: 10.1038/ncb2994. Epub 2014 Jun 29. PMID: 24976383

Learn more
Mitotic wnt signaling promotes protein stabilization and regulates cell size

Acebron SP, Karaulanov E, Berger BS, Huang YL, Niehrs C. Mol Cell. 2014 May 22;54(4):663-74. doi: 10.1016/j.molcel.2014.04.014. Epub 2014 May 15. PMID: 24837680

Learn more