SGO1C is a non-functional isoform of Shugoshin and can disrupt sister chromatid cohesion by interacting with PP2A-B56.
Shugoshin (SGO1) plays a pivotal role in sister chromatid cohesion during mitosis by protecting the centromeric cohesin from mitotic kinases and WAPL. Mammalian cells contain at least 6 alternatively spliced isoforms of SGO1. The relationship between the canonical SGO1A with shorter isoforms including SGO1C remains obscure. Here we show that SGO1C was unable to replace the loss of SGO1A. Instead, expression of SGO1C alone induced aberrant mitosis similar to depletion of SGO1A, promoting premature sister chromatid separation, activation of the spindle-assembly checkpoint, and mitotic arrest. In disagreement with previously published data, we found that SGO1C localized to kinetochores. However, the ability to induce aberrant mitosis did not correlate with its kinetochore localization. SGO1C mutants that abolished binding to kinetochores still triggered premature sister chromatid separation. We provide evidence that SGO1C-mediated mitotic arrest involved the sequestering of PP2A-B56 pool. Accordingly, SGO1C mutants that abolished binding to PP2A localized to kinetochores but did not induce aberrant mitosis. These studies imply that the expression of SGO1C should be tightly regulated to prevent dominant-negative effects on SGO1A and genome instability.
a Division of Life Science; Center for Cancer Research; and State Key Laboratory of Molecular Neuroscience; Hong Kong University of Science and Technology; Kowloon , Hong Kong , China.
Wing Ki
WK
Wong
a Division of Life Science; Center for Cancer Research; and State Key Laboratory of Molecular Neuroscience; Hong Kong University of Science and Technology; Kowloon , Hong Kong , China.
Terrenz
T
Kelly
a Division of Life Science; Center for Cancer Research; and State Key Laboratory of Molecular Neuroscience; Hong Kong University of Science and Technology; Kowloon , Hong Kong , China.
Jingjing
J
Li
a Division of Life Science; Center for Cancer Research; and State Key Laboratory of Molecular Neuroscience; Hong Kong University of Science and Technology; Kowloon , Hong Kong , China.
Hoi Tang
HT
Ma
a Division of Life Science; Center for Cancer Research; and State Key Laboratory of Molecular Neuroscience; Hong Kong University of Science and Technology; Kowloon , Hong Kong , China.
Randy Y C
RY
Poon
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D008941:Spindle Apparatus / Q000378:metabolism
D018797:Cell Cycle Proteins; D020033:Protein Isoforms; C496644:SGO1 protein, human; D054648:Protein Phosphatase 2
Shugoshin; cohesion; kinetochore; mitosis; spindle-assembly checkpoint