Gordon Chan

Biography

Chromosome segregation, kinetochore structure and assembly, mitotic checkpoint control, and chromosome cohesion In my laboratory, research is centered on the mechanism of cell cycle control and particularly the regulation of accurate chromosome segregation during mitosis. The mitotic checkpoint is a failsafe mechanism by which the cell prevents premature anaphase and ensures accurate chromosome segregation. The relevance this line of basic research to cancer is established in the demonstrated importance of chromosome fidelity during cell division to carcinogenesis. 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. We are currently examining 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.

Research Interest

Main research interest is to understand the molecular mechanisms of mitotic checkpoint control in mammalian cells. We propose to examine the mechanism of action of three recently identified checkpoint proteins, roughdeal (hRod), hZw10, and hMPS1. hRod and hZw10 function in two ways during mitosis. Firstly, hRod and hZw10 specify the assembly of the microtubule (MT) motor dynein/dynactin to kinetochores during mitosis. Secondly, hRod and hZw10 are essential components of the mitotic checkpoint and they interact with the checkpoint kinase hBUB1. We propose that hRod/hZw10 and hBUB1 may be part of a mechanosensory complex that monitors kinetochore:MT interactions mediated by the dynein/dynactin complex.