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Elucidating how chromosome cohesion is regulated and established during mammalian meiosis

Objective

Sister chromatid cohesion is essential for proper chromosome segregation. Chromosome cohesion is mediated by cohesin complexes which form a ring-like structure that embraces replicated sister chromatids and hold them together until anaphase onset. Although cohesin binds to DNA dynamically before S phase, cohesion is only established during DNA replication, which requires acetylation of cohesin complexes and subsequent recruitment of Sororin. Sororin promotes cohesion establishment and cohesion maintenance from S phase until mitosis by antagonizing Wapl. Maintenance of chromosome cohesion is extremely important in mammalian meiosis. In oocytes, cohesion establishment occurs during pre-meiotic S phase, which takes place before birth, and then has to be stably maintained until completion of meiosis, which only occurs several months or years later during ovulation. The mechanism responsible for meiotic cohesin stabilization for such long periods of time remains unclear. Notably, the increase of trisomies and other birth defects with maternal age correlates with a gradual loss of sister chromosome cohesion during oocyte maturation. Here, we intend to study how chromosome cohesion is established and regulated during meiosis and to unravel the detailed mechanism responsible for maintenance of sister chromatid cohesion for very long periods of time. We will additionally study how the dynamics of meiotic cohesin complexes affect homologous pairing and meiotic recombination.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/chromosome
  • /natural sciences/biological sciences/genetics and heredity/heredity
  • /social sciences/sociology/demography/fertility

Call for proposal

FP7-PEOPLE-2012-IEF
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Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH
Address
Campus-vienna-biocenter 1
1030 Wien
Austria
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
EU contribution
€ 179 137,20
Administrative Contact
Tanja Winkler (Mrs.)