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OOAGEMEIOSIS

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AGE RELATED CHANGES IN CHROMOSOME SEGREGATION IN FEMALE MEIOSIS

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 siste... ver más

30/11/2011

IAPG

45K€

Presupuesto del proyecto: 45K€

Líder del proyecto

Ustav zivocisne fyziologie a genetiky AV CR,... No se ha especificado una descripción o un objeto social para esta compañía.

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2011-11-30 No tenemos la información de la convocatoria

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IAPG

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Líder del proyecto

Ustav zivocisne fyziologie a genetiky AV CR,... No se ha especificado una descripción o un objeto social para esta compañía.

Presupuesto del proyecto 45K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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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