Role of ubiquitin-protein ligase UBR5 in the disassembly of mitotic checkpoint complexes

Abstract

Significance The mitotic checkpoint system is essential for the prevention of mistakes in the segregation of chromosomes in mitosis. As long as chromosomes are not attached correctly to the mitotic spindle, a mitotic checkpoint complex (MCC) is assembled and inhibits the action of ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome) to initiate anaphase. When the checkpoint is turned off, MCC is disassembled, allowing anaphase initiation. The mechanisms of MCC disassembly have been studied, but the regulation of this process remained obscure. We found that a second ubiquitin ligase, UBR5 (ubiquitin-protein ligase N -recognin 5), ubiquitylates MCC components and stimulates the disassembly of MCC from APC/C, as well as the dissociation of a subcomplex of MCC.