Identification of a Sgo2-Dependent but Mad2-Independent Pathway Controlling Anaphase Onset in Fission Yeast.
The onset of anaphase is triggered by activation of the anaphase-promoting complex/cyclosome (APC/C) following silencing of the spindle assembly checkpoint (SAC). APC/C triggers ubiquitination of Securin and Cyclin B, which leads to loss of sister chromatid cohesion and inactivation of Cyclin B/Cdk1, respectively. This promotes relocalization of Aurora B kinase and other components of the chromosome passenger complex (CPC) from centromeres to the spindle midzone. In fission yeast, this is mediated by Clp1 phosphatase-dependent interaction of CPC with Klp9/MKLP2 (kinesin-6). When this interaction is disrupted, kinetochores bi-orient normally, but APC/C activation is delayed via a mechanism that requires Sgo2 and some (Bub1, Mph1/Mps1, and Mad3), but not all (Mad1 and Mad2), components of the SAC and the first, but not second, lysine, glutamic acid, glutamine (KEN) box in Mad3. These data indicate that interaction of CPC with Klp9 terminates a Sgo2-dependent, but Mad2-independent, APC/C-inhibitory pathway that is distinct from the canonical SAC.
Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK; Institute of Advanced Study, University of Warwick, Coventry CV4 7AL, UK.
John C
JC
Meadows
Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
Theresa C
TC
Lancaster
Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
Graham J
GJ
Buttrick
Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, UK.
Alicja M
AM
Sochaj
Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
Liam J
LJ
Messin
Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
Maria
M
Del Mar Mora-Santos
Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, UK.
Kevin G
KG
Hardwick
Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK. Electronic address: j.millar@warwick.ac.uk.
Jonathan B A
JBA
Millar
D000705:Anaphase; D064173:Anaphase-Promoting Complex-Cyclosome / Q000378:metabolism; D001216:Asparagine / Q000378:metabolism; D064107:Aurora Kinase B / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002503:Centromere / Q000378:metabolism / Q000502:physiology; D019926:Cyclin B / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism / Q000502:physiology; D008239:Lysine / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D012568:Schizosaccharomyces / Q000378:metabolism* / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism / Q000502:physiology
D018797:Cell Cycle Proteins; D019926:Cyclin B; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; D018698:Glutamic Acid; D001216:Asparagine; D064173:Anaphase-Promoting Complex-Cyclosome; D064107:Aurora Kinase B; D008239:Lysine
Mad2; anaphase; fission yeast; kinesin; microtubule; midzone; shugoshin; spindle checkpoint