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Mad2 is required for inhibiting securin and cyclin B degradation following spindle depolymerisation in meiosis I mouse oocytes

Lookup NU author(s): Dr Hayden Homer, Dr Alexander McDougall, Dr Mark Levasseur, Professor Alison Murdoch, Professor Mary Herbert

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Abstract

Mad2 is a pivotal component of the spindle assembly checkpoint (SAC) which inhibits anaphase promoting complex/cyclosome (APC/C) activity by sequestering Cdc20 thereby regulating the destruction of securin and cyclin B. During mitosis, spindle depolymerisation induces a robust Mad2-dependent arrest due to inhibition of securin and cyclin B destruction. In contrast to mitosis, the molecular details underpinning the meiosis I arrest experienced by mouse oocytes exposed to spindle depolymerisation remain incompletely characterised. Notably, the role of Mad2 and the fate of the anaphase-marker, securin, are unexplored. As shown previously, we find that spindle depolymerisation by nocodazole inhibits first polar body extrusion (PBE) and stabilises cyclin B and cyclin-dependent kinase 1 activity in mouse oocytes. Here we show that stabilisation of cyclin B in nocodazole can be sustained for several hours and is associated with stabilisation of securin. These effects are SAC-mediated as, in oocytes depleted of the majority of Mad2 by morpholino antisense, securin and cyclin B are destabilised and 15% of oocytes undergo PBE. This reflects premature APC/C activation as a mutant form of cyclin B lacking its APC/C degradation signal is stable in Mad2-depleted oocytes. Moreover, homologues do not disjoin during the prolonged meiosis I arrest (> 18 h) induced by nocodaozole indicating that a non-cleavage mechanism is insufficient on its own for resolution of arm cohesion in mammalian oocytes. In conclusion, when all kinetochores lack attachment and tension, mouse oocytes mount a robust Mad2-dependent meiosis I arrest which inhibits the destruction of securin and cyclin B. © 2005 Society for Reproduction and Fertility.


Publication metadata

Author(s): Homer HA, McDougall A, Levasseur M, Murdoch AP, Herbert M

Publication type: Article

Publication status: Published

Journal: Reproduction

Year: 2005

Volume: 130

Issue: 6

Pages: 829-843

ISSN (print): 1470-1626

ISSN (electronic): 1741-7899

Publisher: BioScientifica Ltd.

URL: http://dx.doi.org/10.1530/rep.1.00856

DOI: 10.1530/rep.1.00856

PubMed id: 16322543


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