Sds22 and Repo-Man stabilize chromosome segregation by counteracting Aurora B on anaphase kinetochores.
During mitotic spindle assembly, Aurora B kinase is part of an error correction mechanism that detaches microtubules from kinetochores that are under low mechanical tension. During anaphase, however, kinetochore-microtubule attachments must be maintained despite a drop of tension after removal of sister chromatid cohesion. Consistent with this requirement, Aurora B relocates away from chromosomes to the central spindle at the metaphase-anaphase transition. By ribonucleic acid interference screening using a phosphorylation biosensor, we identified two PP1-targeting subunits, Sds22 and Repo-Man, which counteracted Aurora B-dependent phosphorylation of the outer kinetochore component Dsn1 during anaphase. Sds22 or Repo-Man depletion induced transient pauses during poleward chromosome movement and a high incidence of chromosome missegregation. Thus, our study identifies PP1-targeting subunits that regulate the microtubule-kinetochore interface during anaphase for faithful chromosome segregation.
Institute of Biochemistry, Swiss Federal Institute of Technology Zurich, CH-8093 Zurich, Switzerland.
Claudia
C
Wurzenberger
Michael
M
Held
Michael A
MA
Lampson
Ina
I
Poser
Anthony A
AA
Hyman
Daniel W
DW
Gerlich
D000705:Anaphase; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D020090:Chromosome Segregation; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034622:RNA Interference; D008941:Spindle Apparatus / Q000378:metabolism
C509224:CDCA2 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C532764:DSN1 protein, human; D009687:Nuclear Proteins; C509751:PPP1R7 protein, human; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D054645:Protein Phosphatase 1