Mad1 kinetochore recruitment by Mps1-mediated phosphorylation of Bub1 signals the spindle checkpoint
| Autor: | Sue Biggins, Nitobe London |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Mad2
Cell cycle checkpoint Saccharomyces cerevisiae Proteins Mad1 BUB1 Cell Cycle Proteins Saccharomyces cerevisiae Spindle Apparatus Biology Protein Serine-Threonine Kinases Genetics Escherichia coli Phosphorylation Kinetochores Kinetochore Mitotic checkpoint complex Nuclear Proteins Cell Cycle Checkpoints G2-M DNA damage checkpoint Recombinant Proteins Cell biology Spindle checkpoint biological phenomena cell phenomena and immunity Developmental Biology Research Paper Protein Binding Signal Transduction |
| Popis: | The spindle checkpoint is a conserved signaling pathway that ensures genomic integrity by preventing cell division when chromosomes are not correctly attached to the spindle. Checkpoint activation depends on the hierarchical recruitment of checkpoint proteins to generate a catalytic platform at the kinetochore. Although Mad1 kinetochore localization is the key regulatory downstream event in this cascade, its receptor and mechanism of recruitment have not been conclusively identified. Here, we demonstrate that Mad1 kinetochore association in budding yeast is mediated by phosphorylation of a region within the Bub1 checkpoint protein by the conserved protein kinase Mps1. Tethering this region of Bub1 to kinetochores bypasses the checkpoint requirement for Mps1-mediated kinetochore recruitment of upstream checkpoint proteins. The Mad1 interaction with Bub1 and kinetochores can be reconstituted in the presence of Mps1 and Mad2. Together, this work reveals a critical mechanism that determines kinetochore activation of the spindle checkpoint. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|