Cell division in yeast is a highly regulated and well studied event. Various checkpoints are placed throughout the cell cycle to ensure faithful segregation of sister chromatids. Unexpected events, such as DNA damage or oxidative stress, cause the activation of checkpoint(s) and cell cycle arrest. Malfunction of the checkpoints may induce cell death. We previously showed that under oxidative stress, the budding yeast cohesin Mcd1, a homolog of human Rad21, was cleaved by the caspase-like protease Esp1. The cleaved Mcd1 C-terminal fragment was then translocated to mitochondria, causing apoptotic cell death. In the present study, we demonstrated that Bir1 plays an important role in spindle assembly checkpoint and cell death. Similar to H2O2 treatment, deletion of BIR1 using a BIR1-degron strain caused degradation of the securin Pds1, which binds and inactivates Esp1 until metaphase-anaphase transition in a normal cell cycle. BIR1 deletion caused an increase level of ROS and mis-location of Bub1, a major protein for spindle assembly checkpoint. In wild type, Bub1 was located at the kinetochores, but was primarily in the cytoplasm in bir1 deletion strain. When BIR1 was deleted, addition of nocodazole was unable to retain the Bub1 localization on kinetochores, further suggesting that Bir1 is required to activate and maintain the spindle assembly checkpoint. Our study suggests that the BIR1 function in cell cycle regulation works in concert with its anti-apoptosis function.
Keywords: apoptosis, BIR1, cell cycle, oxidative stress, spindle assembly checkpoint
Citation: Ren Q, Liou L-C, Gao Q, Bao X and Zhang Z (2012) Bir1 deletion causes malfunction of the spindle assembly checkpoint and apoptosis in yeast. Front. Oncol. 2:93. doi: 10.3389/fonc.2012.00093
Received: 03 May 2012; Accepted: 22 July 2012;
Published online: 09 August 2012.
Edited by:Frank Madeo, Karl-Franzens-Universität, Austria
Reviewed by:Lisa Bouchier-Hayes, Baylor College of Medicine, USA
Copyright: © 2012 Ren, Liou, Gao, Bao and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Zhaojie Zhang, Department of Zoology and Physiology, University of Wyoming, Laramie, WY 82071, USA. e-mail: firstname.lastname@example.org