Abstract: Cohesin is a protein complex that regulates sister chromatid cohesin during cell division. Malfunction in chromatid cohesin results in chromosome missegregation and aneuploidy. Here, we report that mutations of MCD1 and PDS5, two major components of cohesin in budding yeast, cause apoptotic cell death, which is characterized by externalization of phosphatidylserine at cytoplasmic membrane, chromatin condensation and fragmentation, and ROS production. Microarray analysis suggests that the cell death caused by mutation of MCD1 or PDS5 is due to the internal stress response, contrasting to the environmental or external stress response induced by external stimuli, such as hydrogen peroxide. A common feature shared by the internal stress response and external stress response is the response to stimulus, including response to DNA damage, mitochondria functions, and oxidative stress, which play an important role in yeast apoptotic cell death.