1. Nuclear Pores Protect Genome Integrity by Assembling a Premitotic and Mad1-Dependent Anaphase Inhibitor.
- Author
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Rodriguez-Bravo, Veronica, Maciejowski, John, Corona, Jennifer, Buch, Håkon?Kirkeby, Collin, Philippe, Kanemaki, Masato?T., Shah, Jagesh?V., and Jallepalli, Prasad?V.
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NUCLEAR pore complex , *ANAPHASE , *CHROMOSOMES , *CELL cycle , *UBIQUITIN ligases , *CELLULAR signal transduction - Abstract
Summary: The spindle assembly checkpoint (SAC) delays anaphase until all chromosomes are bioriented on the mitotic spindle. Under current models, unattached kinetochores transduce the SAC by catalyzing the intramitotic production of a diffusible inhibitor of APC/CCdc20 (the anaphase-promoting complex/cyclosome and its coactivator Cdc20, a large ubiquitin ligase). Here we show that nuclear pore complexes (NPCs) in interphase cells also function as scaffolds for anaphase-inhibitory signaling. This role is mediated by Mad1-Mad2 complexes tethered to the nuclear basket, which activate soluble Mad2 as a binding partner and inhibitor of Cdc20 in the cytoplasm. Displacing Mad1-Mad2 from nuclear pores accelerated anaphase onset, prevented effective correction of merotelic errors, and increased the threshold of kinetochore-dependent signaling needed to halt mitosis in response to spindle poisons. A heterologous Mad1-NPC tether restored Cdc20 inhibitor production and normal M phase control. We conclude that nuclear pores and kinetochores both emit “wait anaphase” signals that preserve genome integrity. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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