Cell cycle checkpoint control in C. elegans

Project Summary
Chromosome segregation is precisely controlled to ensure that daughter cells receive the correct number of
chromosomes. Cell cycle checkpoints play an important role in this regulation by monitoring chromosome
behavior and delaying or arresting the cell cycle to correct errors. Despite being characterized almost
exclusively in single cells, the functions of cell cycle checkpoints are perhaps most critical in multicellular
organisms, where chromosomal abnormailities can produce cancer, infertility, miscarriages and birth defects.
As multicellular organisms develop, cells undergo dramatic changes in size, shape, fate, chromosome
structure and cell cycle duration. How the function of cell cycle checkpoints is coordinated with and modulated
by these changes in cellular context are unknown.
We have shown that checkpoint proteins in one biological context can monitor and regulate radically different
chromosome behaviors in a different biological context. By analyzing the function and regulation of essential
checkpoint factors in cells that vary in size, shape, fate, and tissue in C. elegans, we will identify mechanisms,
both common and unique, that guarantee that chromosomes segregate properly in all cell types.
Fundamentally, our future work is focused on addressing two major questions: Does the function of checkpoint
proteins vary depending on their biological context, such that the same proteins appear to have dramatically
different roles? Or are there common fundamental mechanisms that monitor diverse chromosome behaviors to
produce functionally different checkpoint responses?

Grant Number: 5R35GM141835-05
NIH Institute/Center: NIH
Principal Investigator: Needhi Bhalla