title: System-level feedbacks make the anaphase switch irreversible.
abstract: The mitotic checkpoint prevents a eukaryotic cell from commencing to separate its replicated genome into two daughter cells (anaphase) until all of its chromosomes are properly aligned on the metaphase plate, with the two copies of each chromosome attached to opposite poles of the mitotic spindle. The mitotic checkpoint is exquisitely sensitive in that a single unaligned chromosome, 1 of a total of ~50, is sufficient to delay progression into anaphase; however, when the last chromosome comes into alignment on the metaphase plate, the mitotic checkpoint is quickly satisfied, and the replicated chromosomes are rapidly partitioned to opposite poles of the dividing cell. The mitotic checkpoint is also curious in the sense that, before metaphase alignment, chromosomes that are not being pulled in opposite directions by the mitotic spindle activate the checkpoint, but during anaphase, these same tensionless chromosomes can no longer activate the checkpoint. These and other puzzles associated with the mitotic checkpoint are addressed by a proposed molecular mechanism, which involves two positive feedback loops that create a bistable response of the checkpoint to chromosomal tension.
authors: Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom.
authors: Enuo
authors: E
authors: He
authors: Orsolya
authors: O
authors: Kapuy
authors: Raquel A
authors: RA
authors: Oliveira
authors: Frank
authors: F
authors: Uhlmann
authors: John J
authors: JJ
authors: Tyson
authors: Béla
authors: B
authors: Novák
references: Nat Cell Biol. 2010 Feb;12(2):185-92
references: 20081838
references: Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):975-80
references: 12509509
references: Nature. 2004 Mar 4;428(6978):93-7
references: 14961024
references: EMBO J. 2009 Sep 16;28(18):2777-85
references: 19696736
references: Nat Cell Biol. 2003 Mar;5(3):249-54
references: 12598903
references: Mol Biol Cell. 2008 Aug;19(8):3426-41
references: 18480403
references: EMBO J. 2003 Dec 15;22(24):6598-609
references: 14657031
references: Nature. 2009 May 28;459(7246):592-5
references: 19387440
references: FEBS Lett. 2009 Dec 17;583(24):3992-8
references: 19703449
references: Genes Dev. 2003 Oct 15;17(20):2520-5
references: 14561775
references: J Cell Biol. 1995 Aug;130(4):941-8
references: 7642709
references: Biochem Soc Trans. 2010 Oct;38(5):1242-6
references: 20863292
references: Nat Cell Biol. 2000 Aug;2(8):492-9
references: 10934469
references: Science. 2006 Aug 4;313(5787):680-4
references: 16825537
references: Cell. 2006 May 19;125(4):719-32
references: 16713564
references: Cell. 2005 Aug 26;122(4):565-78
references: 16122424
references: Biochem Soc Trans. 2010 Dec;38(6):1660-6
references: 21118144
references: Curr Biol. 2010 Aug 10;20(15):1402-7
references: 20619651
references: Mol Biol Cell. 2011 Apr 15;22(8):1191-206
references: 21325631
references: Nature. 2007 Apr 19;446(7138):921-5
references: 17443186
references: Annu Rev Genet. 2009;43:525-58
references: 19886810
references: Curr Opin Cell Biol. 2009 Dec;21(6):785-95
references: 19846287
references: Curr Biol. 2003 Apr 15;13(8):647-53
references: 12699620
references: Trends Cell Biol. 2006 Jan;16(1):55-63
references: 16337124
references: Nat Cell Biol. 1999 Jun;1(2):82-7
references: 10559878
references: Nature. 2006 Apr 13;440(7086):954-8
references: 16612388
references: Nat Rev Mol Cell Biol. 2007 Oct;8(10):798-812
references: 17848966
references: Science. 2000 May 26;288(5470):1379-85
references: 10827941
references: J Cell Biol. 2002 Jun 24;157(7):1125-37
references: 12070128
references: Curr Biol. 2010 Aug 10;20(15):1396-401
references: 20619650
references: Nature. 1992 Oct 15;359(6396):599-604
references: 1406993
references: Mol Biol Cell. 2004 Aug;15(8):3841-62
references: 15169868
references: J Cell Sci. 1993 Dec;106 ( Pt 4):1153-68
references: 8126097
references: Mol Biol Cell. 2002 Jan;13(1):52-70
references: 11809822
references: Nature. 1995 Feb 16;373(6515):630-2
references: 7854422
references: Trends Cell Biol. 2005 Sep;15(9):486-93
references: 16084093
references: Nat Rev Mol Cell Biol. 2006 Sep;7(9):644-56
references: 16896351
references: Nat Cell Biol. 2007 Jul;9(7):724-8
references: 17603504
references: Nat Cell Biol. 2003 Apr;5(4):346-51
references: 12629549
references: Curr Opin Cell Biol. 2003 Apr;15(2):221-31
references: 12648679
references: Nat Rev Mol Cell Biol. 2007 May;8(5):379-93
references: 17426725