Structural Basis for the Molecular Mechanisms Invo.. (STRUCTMITO)
Structural Basis for the Molecular Mechanisms Involving the Ska Complex in Establishing Stable Kinetochore - Microtubule Attachments
Start date: Apr 1, 2013,
End date: Mar 31, 2017
"Cell division, the accurate transfer of genetic information from one cell generation to the next is the molecular basis of life. A number of mitotic molecular machines involving an extensive network of protein-protein interactions are implicated in regulating cell division.Kinetochore (KT) - Microtubule (MT) attachments are central to the accurate chromosome segregation. Among the KT associated proteins, set of proteins called KMN network (KNL-1-Ndc80-Mis12) provides direct MT interactions. Proteins and protein complexes including the Chromosomal Passenger complex (AuroraB – Survivin – Borealin – INCENP ; CPC), Mps1, Bub1, BubR1, Bub3, Mad1, spindly, dynenin-dynactin and the Anaphase Promoting Complex (APC) regulate correct progression of cell division by participating in the quality control mechanism called the spindle checkpoint ensuring the correct KT-MT attachments. Recently identified Ska complex is emerging as a key player in establishing stable KT-MT attachments and coordinating the timely onset of anaphase by interacting with members of the spindle checkpoint.The key goals of the proposed research are to understand 1.the molecular mechanisms by which the Ska complex stabilizes KT-MT attachments 2.how interaction of the Ska complex with spindle checkpoint components coordinate the timely onset of anaphase?The objectives will be achieved by structurally characterizing intermolecular interactions that involve the Ska complex mainly using X-ray crystallography in combination withnegative stain EM and biochemical/biophysical and cell-based assays."
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