Complex formation between Mad1p, Bub1p and Bub3p is crucial for spindle checkpoint function

Current Biology : CB
D Michelle Brady, Kevin G Hardwick


The spindle checkpoint delays the metaphase to anaphase transition in response to defects in kinetochore-microtubule interactions in the mitotic apparatus (see [1] [2] [3] [4] for reviews). The Mad and Bub proteins were identified as key components of the spindle checkpoint through budding yeast genetics [5] [6] and are highly conserved [3]. Most of the spindle checkpoint proteins have been localised to kinetochores, yet almost nothing is known about the molecular events which take place there. Mad1p forms a tight complex with Mad2p [7], and has been shown to recruit Mad2p to kinetochores [8]. Similarly, Bub3p binds to Bub1p [9] and may target it to kinetochores [10]. Here, we show that budding yeast Mad1p has a regulated association with Bub1p and Bub3p during a normal cell cycle and that this complex is found at significantly higher levels once the spindle checkpoint is activated. We find that formation of this complex requires Mad2p and Mps1p but not Mad3p or Bub2p. In addition, we identify a conserved motif within Mad1p that is essential for Mad1p-Bub1p-Bub3p complex formation. Mutation of this motif abolishes checkpoint function, indicating that formation of the Mad1p-Bub1p-Bub3p complex is a crucial step in the spindle ch...Continue Reading


Apr 20, 2013·Trends in Biochemical Sciences·Luying JiaHongtao Yu
Apr 25, 2003·Biochemical and Biophysical Research Communications·Gil-Ju SeoSeong-Tae Kim
Oct 22, 2003·Archives of Medical Research·Carla S Lopes, Claudio E Sunkel
Dec 11, 2002·Current Opinion in Cell Biology·Hongtao Yu
Feb 13, 2001·Current Opinion in Genetics & Development·K Wassmann, R Benezra
Nov 17, 2001·Current Opinion in Pharmacology·K W WoodJ R Jackson
Jan 25, 2007·Nature Reviews. Molecular Cell Biology·Joanna Bloom, Frederick R Cross
Oct 3, 2002·Nature Reviews. Molecular Cell Biology·Andrea Musacchio, Kevin G Hardwick
Jul 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Marina S Lee, Forrest A Spencer
Apr 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Andreas DoncicNaama Barkai
Apr 12, 2012·Proceedings of the National Academy of Sciences of the United States of America·Soonjoung KimXuelian Luo
Sep 11, 2002·Molecular Biology of the Cell·Cheryl D WarrenForrest A Spencer
Dec 31, 2005·Biology of Reproduction·Marta Sikora-PolaczekMaria A Ciemerych
Feb 28, 2002·Journal of Virology·George J PoggioliKenneth L Tyler
Dec 24, 2005·Journal of Bioinformatics and Computational Biology·Yoshinori TamadaSatoru Miyano
Feb 8, 2011·PLoS Genetics·Greicy H GotoKatsumi Kitagawa
Mar 19, 2014·The Journal of Cell Biology·Edward R BallisterMichael A Lampson
Jul 6, 2014·BioMed Research International·José Henrique TeixeiraHassan Bousbaa
Jun 27, 2014·Chromosoma·Francesca Malvezzi, Stefan Westermann
Dec 11, 2013·Proceedings of the National Academy of Sciences of the United States of America·Fengzhi Jin, Yanchang Wang
Oct 21, 2015·Current Biology : CB·Andrea Musacchio
Nov 20, 2015·Current Genetics·Jagoda AdamczykMaciej Wnuk
May 30, 2015·Molecular Biology of the Cell·Nathaniel I KrefmanGeorjana Barnes
Nov 18, 2003·Annual Review of Genetics·Daniel J Lew, Daniel J Burke


Aug 12, 1988·Cell·R M McCarroll, W L Fangman
Feb 16, 1995·Nature·X Li, R B Nicklas
Dec 1, 1994·Molecular and Cellular Biology·B T RobertsM A Hoyt
Dec 1, 1996·Current Opinion in Cell Biology·A D Rudner, A W Murray
Jan 31, 1997·Science·R B Nicklas
Feb 4, 1998·Trends in Genetics : TIG·Kevin G Hardwick
Mar 7, 1998·Science·L H HwangA W Murray
Jun 12, 1998·The Journal of Cell Biology·J C WatersE D Salmon
Oct 24, 1998·The Journal of Cell Biology·R H ChenA W Murray
Jul 21, 1999·Proceedings of the National Academy of Sciences of the United States of America·M J Martinez-ExpositoP K Sorger
Aug 6, 1999·Molecular Biology of the Cell·R H ChenKevin G Hardwick
Sep 2, 1999·Current Biology : CB·S S Taylor
Mar 8, 2000·The Journal of Cell Biology·Kevin G HardwickA W Murray

Related Concepts

Saccharomyces cerevisiae Proteins
Conserved Sequence
Cell Cycle Proteins
Mitotic Spindle Apparatus
Gene Products, Protein
Mitotic Metaphase
Mitotic Anaphase
Homologous Sequences, Amino Acid

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.