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Chromosome segregation during mitosis and meiosis


Principal Investigator: Juraj Gregan

How does the cell ensure that during cell division each daughter cell inherits one copy of every chromosome? Meiosis is a specialized cell division which produces haploid gametes from diploid cells, how is this reduction of chromosome number achieved? We want to understand how cells accurately segregate their chromosomes during mitosis and meiosis. It is important to understand this process because defects in chromosome segregation (missegregation) during mitosis result in cells with abnormal number of chromosomes. Such cells are hallmarks of cancer. Moreover, defects during meiosis cause miscarriages, infertility and genetic diseases such as Down’s Syndrome

Chromosome segregation during meiosis
The reduction of chromosome number during meiosis is achieved by two successive rounds of chromosome segregation, called meiosis I and meiosis II. While meiosis II is similar to mitosis in that sister kinetochores are bi-oriented and segregate to opposite poles, recombined homologous chromosomes segregate during the first meiotic division. Formation of chiasmata, mono-orientation of sister kinetochores and protection of centromeric cohesion are three major features of meiosis I chromosomes which ensure the reductional nature of chromosome segregation. In our studies we use the fission yeast S. pombe, which is an excellent model organism amenable to both genetic and cell biology techniques, to identify new proteins required for proper segregation of chromosomes during meiosis. In order to decipher molecular functions of identified proteins, we combine biochemical and cell biology techniques. To test the possible functional conservation of identified proteins, we plan to analyze the function of the respective homologs in mammalian cells.

Chromosome segregation during mitosis.
Accurate chromosome segregation in mitosis depends on the establishment of correct (amphitelic) kinetochore orientation. Merotelic kinetochore orientation is an error which occurs when a single kinetochore is attached to microtubules emanating from opposite spindle poles. Recent studies showing that merotelic kinetochore attachment represents a major mechanism of aneuploidy in mitotic cells and is the primary mechanism of chromosomal instability in cancer cells underline the importance of studying merotely. We focus on fission yeast proteins required to prevent and correct merotelic attachments in order to understand how cells ensure high fidelity of chromosome segregation.