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Project Information
Project Title:  The role of the zw10/rod complex in mitotic checkpoint regulation of chromosome segregation
Period:  from: 2002-10-01 to: 2007-09-30  
Principal Investigator(s): Chan, Gordon Ka Tun  
Co-Investigators:  
Supervisors:  
Previous Investigators/Supervisors:  
Institution: Alberta Health Services  
Department: Experimental Oncology 
Agency: Canadian Institutes of Health Research 
Program: Operating Grant 
Keywords: BIOCHEMISTRY, BIOCHIMIE, BIOLOGIE CELLULAIRE, CANCER, CELL BIOLOGY, CELL CYCLE REGULATION, CENTROMERE, KINETOCHORE, MITOSIS, MITOTIC CHECKPOINT, MULTIPLE RELEVANCE, PROTEIN-PROTEIN INTERACTION, SE RAPPORTANT A PLUSIEURS 
Abstract: The relevance this application to cancer is established in the demonstrated importance of chromosome fidelity during cell division to carcinogensis. Somatic mutations of mitotic checkpoint genes have been identified and postulated to be important for the chromosome instability phenotype in colorectal cancers. By investigating the molecular mechanism of the mitotic checkpoint, we can better evaluate these genes as potential cancer drug targets as well as contributing to the basic understanding of cancer. This application proposes to examine the mechanisms by which mitotic checkpoint proteins monitor kinetochore:microtubule attachments to ensure that cells with misaligned chromosomes are provided extra time to establish proper connections to the spindle. hZw10 and hRod are kinetochore proteins that recruit dynein/dynactin to kinetochores but were found to be also essential for the mitotic checkpoint. We propose that hZw10 and hRod links kinetochore:microtubule attachments mediated by dynein to the checkpoint. The connection with the checkpoint maybe mediated through hBUB1 as we found that it is part of the hZw10/hRod complex. As hZw10/hRod are conserved only amongst metazoans, their analysis should reveal features of the checkpoint mechanism that are distinct from yeast. 

Funding Information
Fiscal Year Amount
2002-03 $96,539
2003-04 $84,390
2004-05 $84,390
2005-06 $92,738
2006-07 $101,085
2007-08 $50,542
Total: $509,684