Preventing Fatal Destruction: Inhibitors of the Anaphase-Promoting Complex in Meiosis

 Abstract

The anaphase-promoting complex/cyclosome (APC/C) is a multi-subunit ubiquitinligase whose major functions in the cell cycle are the initiation of sister chromatid separation and the inactivation of cyclin-dependent kinases. This complex is also essential for meiosis, a specialised form of the cell cycle characterised by two consecutive rounds of chromosome segregation. To ensure a proper meiotic cell cycle, the activity of APC/C needs to be tightly controlled. It is now evident that inhibitors of APC/C play pivotal roles to avert its untimely activation. During prophase I, this ubiquitin-ligase must be kept inactive to prevent precocious sister chromatid separation. Studies in yeast showed that this inhibition is mediated by a specific subunit of the complex. Accurate chromosome segregation in meiosis I depends on spindle checkpoint proteins such as Mad2 which delay APC/C activation in response to an erroneous spindle attachment of chromosomes. Additional APC/C antagonists are known to block complete cyclin destruction between meiosis I and II, thereby ensuring that cyclin dependent kinases remain active and that DNA replication does not occur. Inhibitors of APC/C also mediate the cytostatic factor induced metaphase II arrest of oocytes. This review highlights the current knowledge about the role and relevance of these diverse regulators of the meiotic APC/C.

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Pages
405 - 415
doi
10.4161/cc.5.4.2476
Type
Review
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Preventing Fatal Destruction: Inhibitors of the Anaphase-Promoting Complex in Meiosis