Co-workers:

Cell division, the accurate transfer of genetic information from one cell generation to the next is the molecular basis of life. A number of molecular machines involving an extensive network of protein-protein interactions are implicated in regulating cell division. The kinetochore is one such molecular machine that physically connects the centromeric region of the chromosomes to the spindle microtubules. Among the 100 different kinetochore associated proteins, a set of proteins called the KMN network (KNL1-Ndc80-Mis12) together with a recently identified Ska complex provides a direct binding site for microtubules. Proteins and protein complexes including the Chromosomal Passenger Complex (AuroraB-Survivin-Borealin-INCENP; CPC), Mps1, Bub1, BubR1, Bub3, Mad1, spindly, dynein-dynactin and the Anaphase Promoting Complex (APC) regulate correct progression of cell division by participating in the quality control mechanism called the spindle checkpoint. 

Understanding the molecular mechanisms of accurate chromosome segregation is crucial, as defects in segregation lead to chromosome instability (CIN), which has direct implications in cancer. In addition to its role in cancer, inaccurate chromosome segregation is implicated in Down's syndrome and Alzheimer’s disease. 

We have been interested in understanding how structural frameworks of inter-molecular interactions at the kinetochore, facilitate kinetochore-microtubule attachment and accurate chromosome segregation. Obtaining the mechanistic details of accurate chromosome segregation using structural approach will improve our understanding of the cell biology of mitosis and allow us to explore the possibilities of targeting specific kinetochore proteins in order to impact on human health.  Our work will mainly involve structural (X-ray crystallography) and biochemical characterization of  key mitotic protein complexes followed by functional evaluations using cell biological methods.

Selected publications:

[1] Jeyaprakash, A. A., Klein, U. R., Lindner, D., Ebert, J., Nigg, E. A. and Conti,  E.  Structure of a Survivin-Borealin-INCENP Core Complex Reveals How Chromosomal Passengers Travel Together. Cell (2007) 131, 271-285
[2] Gaitanos, T. N., Santamaria, A., Jeyaprakash, A. A., Wang, B., Conti, E. and Nigg, E. A. Stable kinetochore-microtubule interactions depend on the Ska complex and its new component Ska3/C13Orf3. EMBO J (2009) 28:1442-1452.

[3] Jeyaprakash, A. A., Basquin, C., Jayachandran, U and Conti, E. Structural Basis or the Recognition of Phosphorylated Histone H3 by the Survivin  Subunit of the Chromosomal Passenger Complex. Structure (2011) 19, 1625-34.