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PMID: 10329618 Published · ppublish English Journal Article

Sister chromatid separation and chromosome re-duplication are regulated by different mechanisms in response to spindle damage.

The EMBO journal ·Vol. 18 ·No. 10 ·1999-05-17 ·Pages 2707-21

Alexandru G, Zachariae W, Schleiffer A, Nasmyth K

Abstract

In yeast, anaphase entry depends on Pds1 proteolysis, while chromosome re-duplication in the subsequent S-phase involves degradation of mitotic cyclins such as Clb2. Sequential proteolysis of Pds1 and mitotic cyclins is mediated by the anaphase-promoting complex (APC). Lagging chromosomes or spindle damage are detected by surveillance mechanisms (checkpoints) which block anaphase onset, cytokinesis and DNA re-replication. Until now, the MAD and BUB genes implicated in this regulation were thought to function in a single pathway that blocks APC activity. We show that spindle damage blocks sister chromatid separation solely by inhibiting APCCdc20-dependent Pds1 proteolysis and that this process requires Mad2. Blocking APCCdh1-mediated Clb2 proteolysis and chromosome re-duplication does not require Mad2 but a different protein, Bub2. Our data imply that Mad1, Mad2, Mad3 and Bub1 regulate APCCdc20, whereas Bub2 regulates APCCdh1.

MeSH Terms
Anaphase Anaphase-Promoting Complex-Cyclosome Calcium-Binding Proteins/metabolism Carrier Proteins Cell Cycle Cell Cycle Proteins/genetics,metabolism Chromosomal Proteins, Non-Histone Cyclin B Cyclins/metabolism DNA Replication/genetics Fungal Proteins/genetics,metabolism GTP-Binding Proteins/metabolism Interphase/genetics Ligases/metabolism Mad2 Proteins Mitosis Monomeric GTP-Binding Proteins Mutation Nocodazole/pharmacology Nuclear Proteins/genetics Phosphoproteins Repressor Proteins Saccharomyces cerevisiae Proteins Schizosaccharomyces pombe Proteins Securin Sister Chromatid Exchange Spindle Apparatus/genetics Ubiquitin-Protein Ligase Complexes Ubiquitin-Protein Ligases Yeasts
Chemicals
BUB2 protein, S cerevisiae Byr4 protein, S pombe CLB2 protein, S cerevisiae Calcium-Binding Proteins Carrier Proteins Cell Cycle Proteins Chromosomal Proteins, Non-Histone Cyclin B Cyclins Fungal Proteins MAD2 protein, S cerevisiae MCD1 protein, S cerevisiae Mad2 Proteins Nuclear Proteins PDS1 protein, S cerevisiae Phosphoproteins Repressor Proteins Saccharomyces cerevisiae Proteins Schizosaccharomyces pombe Proteins Securin TEM1 protein, S cerevisiae mad2 protein, S pombe Ubiquitin-Protein Ligase Complexes Anaphase-Promoting Complex-Cyclosome Ubiquitin-Protein Ligases GTP-Binding Proteins Monomeric GTP-Binding Proteins Ligases Nocodazole
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Alexandru G
Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Zachariae W
Schleiffer A
Nasmyth K
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/18.10.2707
Published
1999-05-17
Pages
2707-21
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1171353
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/18.10.2707 PMC Full Text View journal details
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