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

Marina S. Lee, Forrest A. Spencer

Research output: Contribution to journalArticlepeer-review

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 mad1Δ synthetic lethal screen identified 16 genes whose deletion in cells lacking MAD1 results in death or slow growth. Eleven of these mad1Δ genetic interaction partners encode proteins at the kinetochore-microtubule interface. Analysis of the entire panel revealed similar phenotypes in combination with mad2Δ. In contrast, 13 panel mutants exhibited a less severe phenotype in combination with mad3Δ. 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.

Original languageEnglish (US)
Pages (from-to)10655-10660
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number29
DOIs
StatePublished - Jul 20 2004

ASJC Scopus subject areas

  • General

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