Regulation of chromosome segregation in mitosis and meiosis

Adele Marston, Brian Lee, Brendan Kiburz and Angelika Amon 

Center for Cancer Research
Howard Hughes Medical Institute
Massachusetts Institute of Technology E17-233A
40 Ames Street
Cambridge MA, 02139 

Introduction
Meiosis is a specialized cell cycle that leads to the formation of gametes. Defects in meiotic chromosome segregation are the leading cause of miscarriages and one of the leading causes of birth defects in humans. Understanding how meiotic chromosome segregation is regulated and how the mitotic chromosome segregation cycle is modulated to bring about the specialized meiotic chromosome segregation program is, thus, crucial if we were to uncover the molecular causes of chromosome mis-segregation during meiosis. 

Results
We have conducted a screen in budding yeast to identify all non-essential genes required for faithful meiotic chromosome segregation. This screen was primarily aimed at identifying genes that ensure that cohesin complexes which keep sister chromatids together are lost in a stepwise manner in meiosis. Indeed, we identified three kinetochore proteins essential for retaining centromeric cohesion during meiosis I. We also characterized the role of the Polo kinase Cdc5 during meiosis. The protein kinase regulates cohesion removal, kinetochore orientation and spindle disassembly during meiosis I. Thus, our results indicate that Cdc5 is a key determinant of the meiosis I chromosome segregation program.

Reference 

Lee, B.H. and Amon, A. (2003).  Role of Polo-like kinase CDC5 in programming meiosis I chromosome segregation.   Science 300, 482-486.