Area B: Biological Targets B6: Targeting centromer recuitment of mitotic regulators by supramolecular ligands

Project B6 will exploit supramolecular modulators to interfere with the role of phosphorylation in chromosome passenger complex (CRC) localization during mitosis. Chemical tools will be specifically directed against the ionic interaction between Survivin and phosphorylated Histone H3; they will also be utilized to target more complex interactions, in particular those between the CPC and reconstituted nucleosomes. Similarly, protein-protein interactions between the Bub1:Bub3 complex and phosphorylated MELT repeats in Spc105 or Knl1 will be disrupted by tailored ligands to also address the importance of this interaction for chromosome passenger complex recruitment and kinetochore function. 

Curriculum Vitae

Professional career

Scientific education and degrees

Selected Publications

S. Mosalaganti, J. Keller, A. Altenfeld, M. Winzker, P. Rombaut, M. Saur, A. Petrovic, A. Wehenkel, S. Wohlgemuth, F. Müller, S. Maffini, T. Bange, F. Herzog, H. Waldmann, S. Raunser, A. Musacchio: Structure of the RZZ complex and molecular basis of its interaction with Spindly. J Cell Biol. 2017, 216:961-981.

A. C. Faesen, M. Thanasoula, S. Maffini, C. Breit, F. Müller, S. van Gerwen, T. Bange, A. Musacchio: Basis of catalytic assembly of the mitotic checkpoint complex. Nature. 2017, 542:498-502.

D. Pan, K. Klare, A. Petrovic, A. Take, K. Walstein, P. Singh, A. Rondelet, A.W. Bird, A. Musacchio: CDK-regulated dimerization of M18BP1 on a Mis18 hexamer is necessary for CENP-A loading. Elife. 2017 6. pii: e23352.

A. Petrovic, J. Keller, Y. Liu, K. Overlack, J. John, Y. Dimitrova, S. Jenni, S. van Gerwen, P. Stege, S. Wohlgemuth, P. Rombaut, F. Herzog, S.C. Harrison, I. Vetter, A. Musacchio: Structure of the MIS12 complex and molecular basis of its interaction with CENP-C at human kinetochores. Cell. 2016, 167:1020-1040.

J. R. Weir, A. C. Faesen, K. Klare, A. Petrovic, F. Basilico, J. Fischböck, S. Pentakota, J. Keller, M. E. Pesenti, D. Pan, D. Vogt, S. Wohlgemuth, F. Herzog, A. Musacchio: Insights from biochemical reconstitution into the architecture of human kinetochores. Nature. 2016, 537:249-253.

K. Overlack, I. Primorac, M. Vleugel, V. Krenn, S. Maffini, I. Hoffmann, G. J. Kops, A. Musacchio: A molecular basis for the differential roles of Bub1 and BubR1 in the spindle assembly checkpoint. Elife. 2015, 4:e05269.

K. Klare, J. R. Weir, F. Basilico, T. Zimniak, L. Massimiliano, N. Ludwigs, F. Herzog, A. Musacchio: CENP-C is a blueprint for constitutive centromere-associated network assembly within human kinetochores. J Cell Biol. 2015, 210:11-22. jcb.201412028.

A. Petrovic, S. Mosalaganti, J. Keller, M. Mattiuzzo, K. Overlack, V. Krenn, A. De Antoni, S. Wohlgemuth, V. Cecatiello, S. Pasqualato, S. Raunser, A. Musacchio: Modular Assembly of RWD Domains on the Mis12 Complex Underlies Outer Kinetochore Organization. Mol. Cell. 2014, 53:591-605.

G. M. Alushin, V. H. Ramey, S. Pasqualato, D. A. Ball, N.Grigorieff, A. Musacchio, E. Nogales: The Ndc80 kinetochore complex forms oligomeric arrays along microtubules. Nature. 2010, 467:805-10.

C. Ciferri, S. Pasqualato, E. Screpanti, G. Varetti, S. Santaguida, G. Dos Reis, A. Maiolica, J. Polka, J. G. De Luca, P. De Wulf, M. Salek, J. Rappsilber, C. A.Moores, E. D. Salmon, A. Musacchio: Implications for kinetochore-microtubule attachment from the structure of an engineered Ndc80 complex. Cell. 2008, 133, 427-439