Document Detail


A Saccharomyces cerevisiae mutant strain defective in acetyl-CoA carboxylase arrests at the G2/M phase of the cell cycle.
MedLine Citation:
PMID:  12626751     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To elucidate the essential functions of acetyl-CoA carboxylase (ACC1FAS3) in Saccharomyces cerevisiae, a temperature-sensitive mutant (acc1(ts)) was constructed. When the acc1(ts) cells were synchronized in G(1) phase with alpha-factor at the permissive temperature of 24 degrees C and then released from the blockade and incubated at the restrictive temperature of 37 degrees C, 95% of the cell population became arrested at the G(2)M phase of the cell cycle despite the presence of fatty acids (C(14)-C(26)) in the medium. These cells developed large undivided nuclei, and the spindles of the arrested mutant cells were short. Shifting the G(2) arrested cells back to the permissive temperature resulted in a reversal of the cell-cycle arrest, with cells initiating mitosis. However, after 3 h of incubation at 37 degrees C, G(2) arrested mutant cells lost viability and displayed a uniquely altered nuclear envelope. Using [1-(14)C]acetate as a precursor for fatty acids synthesis, we identified the phospholipids and sphingolipids derived from acc1(ts) cells and wild-type cells at 24 degrees C and 37 degrees C, respectively. The levels of inositol-ceramides [IPC, MIPC, and M(IP)(2)C] and very long-chain fatty acids C(24) and C(26) declined sharply in the G(2)M arrested cells because of ACC inactivation. Shifting the acc1(ts) cells to 24 degrees C after 2 h of incubation at 37 degrees C resulted in reactivation of the ACC and elevation of the ceramides and very long-chain fatty acid syntheses with normal cell-cycle progression. In contrast, synthesis of wild-type inositol-ceramides, C(24) and C(26), fatty acids were elevated on incubation at 37 degrees C and declined when the cells shifted to the permissive temperature of 24 degrees C.
Authors:
Walid Al-Feel; James C DeMar; Salih J Wakil
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2003-03-07
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  100     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-03-19     Completed Date:  2003-04-21     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3095-100     Citation Subset:  IM    
Affiliation:
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetyl-CoA Carboxylase / genetics*,  metabolism
Ceramides / metabolism
G2 Phase
Genes, Fungal
Lipid Metabolism
Microscopy, Electron
Mitosis
Mutation
Nuclear Envelope / ultrastructure
Phenotype
Saccharomyces cerevisiae / cytology,  enzymology*,  genetics*
Temperature
Grant Support
ID/Acronym/Agency:
GM 19091/GM/NIGMS NIH HHS; GM 63115/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Ceramides; EC 6.4.1.2/Acetyl-CoA Carboxylase
Comments/Corrections

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