Back to Search
Start Over
Nuclear Pores Protect Genome Integrity by Assembling a Premitotic and Mad1-Dependent Anaphase Inhibitor.
- Source :
-
Cell . Feb2014, Vol. 156 Issue 5, p1017-1031. 15p. - Publication Year :
- 2014
-
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]
Details
- Language :
- English
- ISSN :
- 00928674
- Volume :
- 156
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 94687122
- Full Text :
- https://doi.org/10.1016/j.cell.2014.01.010