Project (Holger Bastians)
Chromosomal instability (CIN) is a major hallmark of human cancer and is defined as an increased rate of whole chromosome missegregation during mitotic cell division leading to aneuploidy and high genetic heterogeneity. Thus, CIN is a driving force for tumor evolution and contributes to tumor progression and to the development of therapy resistance. Our lab is interested in the molecular mechanisms causing CIN. Recently, we discovered that abnormal microtubule dynamics specifically within mitotic spindles comprise a key mechanism causing CIN. We are now aiming at identifying and characterizing cancer-relevant genes and pathways (e.g. the Wnt pathway or pathways related to DNA replication) that mediate this important cellular phenotype causing genome instabilty. For this, we will employ cell biological and microscopy-based techniques to unravel the molecular mechanisms for abnormal microtubule dynamics in mitotic cells as a a basis for genome instability in cancer. The planned project will also be associated to our recently established germany-wide collaborative research unit 2800, which focusses on the cross-talks between DNA replication and mitosis (www.for2800.de).
Homepage Research Group
Böhly, N., Kistner, M. and H. Bastians. (2019). Mild replication stress causes aneuploidy by deregulating microtubule dynamics in mitosis. Cell Cycle 18:2770-2783.
Ertych, N., Stolz, A., Valerius, O., Braus, G.H. and H. Bastians. (2016). The CHK2-BRCA1 tumor suppressor axis restrains oncogenic AURORA-A to ensure proper mitotic microtubule assembly. Proc. Nat. Acad. Sci. USA. 113:1817-1822.
Ertych, N., A. Stolz, A. Stenzinger, W. Weichert, S. Kaulfuß, B. P., A. Aigner, L. Wordeman, and H. Bastians. (2014). Increased microtubule assembly rates influence chromosomal instability in colorectal cancer. Nature Cell Biology. 16:779-791.
Stolz, A., N. Ertych, A. Kienitz, C. Vogel, V. Schneider, B. Fritz, R. Jacob, G. Dittmar, W. Weichert, I. Petersen, and H. Bastians. (2010). The CHK2-BRCA1 tumour suppressor pathway ensures chromosomal stability in human somatic cells. Nature Cell Biology. 12:492-499.