Bipolar orientation of chromosomes in Saccharomyces cerevisiae is monitored by Mad1 and Mad2, but not by Mad3

Proceedings of the National Academy of Sciences of the United States of America
Marina S Lee, F Spencer

Abstract

The spindle checkpoint governs the timing of anaphase separation of sister chromatids. In budding yeast, Mad1, Mad2, and Mad3 proteins are equally required for arrest in the presence of damage induced by antimicrotubule drugs or catastrophic loss of spindle structure. We find that the MAD genes are not equally required for robust growth in the presence of more subtle kinetochore and microtubule damage. A mad1Delta synthetic lethal screen identified 16 genes whose deletion in cells lacking MAD1 results in death or slow growth. Eleven of these mad1Delta genetic interaction partners encode proteins at the kinetochore-microtubule interface. Analysis of the entire panel revealed similar phenotypes in combination with mad2Delta. In contrast, 13 panel mutants exhibited a less severe phenotype in combination with mad3Delta. Checkpoint arrest in the absence of bipolar orientation and tension (induced by replication block in a cdc6 mutant) was lacking in cells without MAD1 or MAD2. Cells without MAD3 were checkpoint-proficient. We conclude that Mad1 and Mad2 are required to detect bipolar orientation and/or tension at kinetochores, whereas Mad3 is not.

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Citations

Nov 4, 2005·Molecular Biology of the Cell·Cory D DunnRobert E Jensen
Mar 30, 2007·Molecular Biology of the Cell·Victoria E AndersonKevin G Hardwick
Jul 17, 2009·Molecular Biology of the Cell·Tessie M NgSue Biggins
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Jun 26, 2015·FEMS Microbiology Reviews·Adrianna SkonecznaMarek Skoneczny
Feb 3, 2005·Yeast
May 12, 2005·Cell Motility and the Cytoskeleton·Sheila Kadura, Shelley Sazer
Oct 25, 2012·Journal of Cell Science·Scott C SchuylerVivian Jen-Wei Kuan

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