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PMID: 9223296 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The Schizosaccharomyces pombe spindle checkpoint protein mad2p blocks anaphase and genetically interacts with the anaphase-promoting complex.

He X, Patterson TE, Sazer S

Abstract

The spindle checkpoint monitors mitotic spindle integrity and the attachment of kinetochores to the spindle. Upon sensing a defect the checkpoint blocks cell cycle progression and thereby prevents chromosome missegregation. Previous studies in budding yeast show that the activated spindle checkpoint inhibits the onset of anaphase by an unknown mechanism. One possible target of the spindle checkpoint is anaphase promoting complex (APC), which controls all postmetaphase events that are blocked by spindle checkpoint activation. We have isolated mad2, a spindle checkpoint component in fission yeast, and shown that mad2 overexpression activates the checkpoint and causes a cell cycle arrest at the metaphase-to-anaphase transition. In addition to the observation that mad2-induced arrest can be partially relieved by mitosis-promoting factor inactivation, we present genetic evidence consistent with the hypothesis that the spindle checkpoint imposes a cell cycle arrest by inhibiting APC-dependent proteolysis.

MeSH Terms
Amino Acid Sequence Anaphase/genetics Anaphase-Promoting Complex-Cyclosome Calcium-Binding Proteins/genetics,metabolism Carrier Proteins Cell Cycle Proteins DNA, Complementary Fungal Proteins/genetics,metabolism Ligases/genetics,metabolism Mad2 Proteins Maturation-Promoting Factor/antagonists & inhibitors Metaphase/genetics Molecular Sequence Data Nuclear Proteins Protein Binding Schizosaccharomyces/cytology,genetics,metabolism Schizosaccharomyces pombe Proteins Sequence Homology, Amino Acid Spindle Apparatus Ubiquitin-Protein Ligase Complexes Ubiquitin-Protein Ligases
Chemicals
Calcium-Binding Proteins Carrier Proteins Cell Cycle Proteins DNA, Complementary Fungal Proteins Mad2 Proteins Nuclear Proteins Schizosaccharomyces pombe Proteins mad2 protein, S pombe Ubiquitin-Protein Ligase Complexes Anaphase-Promoting Complex-Cyclosome Ubiquitin-Protein Ligases Maturation-Promoting Factor Ligases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
He X
Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Patterson T E
Sazer S
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1997-07-22
Pages
7965-70
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC21538
Subset
IM
Grants
NIA NIH HHS · T32 AG000183 · United States
Intramural NIH HHS · Z01 AG000183 · United States
NIGMS NIH HHS · GM49119 · United States
Databases
GENBANK
U72150
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