| First Author | Fava LL | Year | 2011 |
| Journal | EMBO J | Volume | 30 |
| Issue | 16 | Pages | 3322-36 |
| PubMed ID | 21772247 | Mgi Jnum | J:176014 |
| Mgi Id | MGI:5288122 | Doi | 10.1038/emboj.2011.239 |
| Citation | Fava LL, et al. (2011) Probing the in vivo function of Mad1:C-Mad2 in the spindle assembly checkpoint. EMBO J 30(16):3322-36 |
| abstractText | The spindle assembly checkpoint (SAC) restrains anaphase until all chromosomes become bi-oriented on the mitotic spindle. The SAC protein Mad2 can fold into two distinct conformers, open (O) and closed (C), and can asymmetrically dimerize. Here, we describe a monoclonal antibody that specifically recognizes the dimerization interface of C-Mad2. This antibody revealed several conformation-specific features of Mad2 in human cells. Notably, we show that Mad2 requires association with Mad1 to adopt the closed conformation and that the activity of the Mad1:C-Mad2 complex undergoes regulation by p31comet-dependent 'capping'. Furthermore, C-Mad2 antibody microinjection caused an abrupt termination of the SAC and accelerated mitotic progression. Remarkably, microinjection of a Mad1-neutralizing antibody triggered a comparable mitotic acceleration. Our study provides direct in vivo evidence for the model that a kinetochore complex of Mad1:C-Mad2 acts as a template to sustain the SAC and it challenges the distinction between SAC and mitotic timer. |
