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Inhibitory Phosphorylation Of Separase Is Essential For Genome Stability And Viability Of Murine Embryonic Germ Cells

Higher eukaryotes rely on a separate cell lineage, the germline, to pass genetic information from generation to generation.  To ensure faithful transmission of genetic information, cell cycle checkpoint mechanisms are engaged during mitotic and meiotic divisions of germ cells.

The identity and function of these checkpoints is not well understood. In mammals, the germline is specified early in embryogenesis as primordial germ cells (PGCs) at the epiblast stage (around embryonic day 5.0 in mice). PGCs then migrate out from their birthplace and arrive at the genital ridge several days later. In the genital ridge, PGCs undergo a great expansion in number through mitosis.

During this expansion, PGCs critically depend on the inhibitory phosphorylation of separase to prevent premature separation of sister chromatids and hence progeny with abnormal chromosome number. Separase is a protease which cleaves the Scc1 subunit of sister chromatid cohesin complex. Its activity must be suppressed before all sisters are aligned at the metaphase plate. Two mechanisms are known that can inhibit separase: phosphorylation and binding by securin, both of which are activated at the spindle assembly checkpoint.

Published this week in the open-access journal PLoS Biology, Xingxu Huang, Pumin Zhang, and colleagues show how although these two mechanisms are redundant in somatic cells. Their results indicate that the inhibitory phosphorylation of separase is uniquely required in the germline. 

Inhibitory phosphorylation of separase is essential for genome stability and viability of murine embryonic germ cells.
Huang X, Andreu-Vieyra CV, York JP, Hatcher R, Lu T (2008)
PLoS Biol 6(1): e15. doi:10.1371/journal.pbio.0060015
Click here to view article online

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Inhibitor de fosforilare de Separase genomul este esenþialã pentru stabilitatea ºi viabilitatea germene celulele embrionare murine - Inhibitory Phosphorylation Of Separase Is Essential For Genome Stability And Viability Of Murine Embryonic Germ Cells - articole medicale engleza - startsanatate