Molecular analysis of Structural Maintenance of Chromosome (SMC) proteins at the kinetochore

Cell division is a remarkable process in which a cell grows and divides to form two identical daughter cells. For this to occur, cell has to accomplish two major tasks a) Duplicate the DNA ( DNA replication) b) Segregate the duplicated DNA molecules equally to the 2 daughter cells( chromosome segregation). Mistakes in either process can lead to cancer and disease in humans. Structural maintenance of chromosome (SMC) proteins is a family of proteins conserved from bacteria to humans and essential for accurate chromosome segregation.. Members of the SMC family play crucial roles in organizing the higher order structure of chromosomes. But the precise function of these proteins are poorly understood. Our research aims to uncover the function of this important class of proteins using the 'baker's yeast' as the model system. Since cell division is vital for all forms of life mechanisms that mediate high-fidelity chromosome segregation are generally conserved from yeast to humans.

Structural Maintenance of Chromosome(SMC) family of proteins are involved in diverse processes like sister chromatid cohesion( Cohesin), chromosome condensation ( Condensin) and DNA repair ( Smc5/6). One of the striking features of all SMC complexes is that they are enriched at centromeric regions. But how SMC complexes are enriched at pericentric regions and the functional significance of this localized enrichment is poorly understood. We would like to a) identify kinetochore factors required for pericentric cohesin binding using a functional assay for cohesin in Saccharomyces cerevisiae b) test whether the identified kinetochore factors are also required for cohesin binding to the centromeric regions in Schizosaccharomyces pombe and pericentric binding of SMC5/6 complex c)unravel the functional significance of pericentric SMC complexes by examining the consequences of cleavage of centromeric SMC complexes. Our research proposes to dissect the relationship between two conserved components critical for chromosome segregation, namely the SMC proteins and the kinetochore.