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Start date: 01 Dec 2008, End date: 30 Nov 2011 PROJECT  FINISHED 

Gametes are produced in reduction division called meiosis, in which cells undergo one round of DNA replication followed by two successive chromosome segregations. Homologue chromosomes are segregated in first meiosis whereas sister chromatids are separated in second meiosis. Actual chromosome segregation is preceded by recombination and exchange of genetic material. In human, meiosis is associated with a surprisingly high incidence of errors, leading to numerical chromosomal aberrations, which are more prevalent in female gametes and seem to increase with maternal age. Oocyte aneuploidy has severe consequences including pregnancy loss, birth defects and mental retardation. It was shown that the cohesin complex, holding together sister chromatids, is vital for faithful chromosome segregation in meiosis as well as in mitosis. In meiosis, the cohesin complexes have to be removed sequentially from chromosomes. The enzyme separase, responsible for cohesin cleavage, is temporarily activated in both divisions, cleaving the arm cohesion in first and centromeric cohesion in the second division. Centromeric cohesion, essential for accurate segregation of sister chromatids, is protected by proteins called shugoshin or Sgo1/Sgo1 and phosphatase 2A (PP2A) against cleavage by separase. The errors in sequential removal of cohesin might play a key role in mechanism of age-related aneuploidy in oocytes. We would like to develop a system, which would allow us to study the changes of expression and distribution of molecules involved in removal or protection of cohesin complexes during mammalian meiosis. Our results will greatly aid understanding to the molecular mechanisms underlying changes in chromosome segregation related to age in mammalian meiosis.
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