Nuclear pores protect genome integrity by assembling a premitotic and mad1-dependent anaphase inhibitor Journal Article
| Authors: | Rodriguez Bravo, V.; Maciejowski, J.; Corona, J.; Buch, H. K.; Collin, P.; Kanemaki, M. T.; Shah, J. V.; Jallepalli, P. V. |
| Article Title: | Nuclear pores protect genome integrity by assembling a premitotic and mad1-dependent anaphase inhibitor |
| Abstract: | 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. © 2014 Elsevier Inc. |
| Keywords: | signal transduction; controlled study; human cell; protein function; protein localization; mitosis; protein binding; regulatory mechanism; protein transport; cytoplasm; anaphase; mitosis spindle; cell cycle m phase; cell cycle regulation; centromere; cell cycle protein 20; protein mad2; interphase; nuclear pore complex; protein mad1; human; priority journal; article |
| Journal Title: | Cell |
| Volume: | 156 |
| Issue: | 5 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2014-02-27 |
| Start Page: | 1017 |
| End Page: | 1031 |
| Language: | English |
| DOI: | 10.1016/j.cell.2014.01.010 |
| PROVIDER: | scopus |
| PMCID: | PMC3947552 |
| PUBMED: | 24581499 |
| DOI/URL: | |
| Notes: | Cited By (since 1996):1 -- Export Date: 2 April 2014 -- CODEN: CELLB -- Source: Scopus |
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