Document Detail

Diminishing HDACs by drugs or mutations promotes normal or abnormal sister chromatid separation by affecting APC/C and adherin.
MedLine Citation:
PMID:  18354085     Owner:  NLM     Status:  MEDLINE    
Histone acetyltransferases (HATs) and histone deacetylases (HDACs) play important roles in cell regulation, including cell cycle progression, although their precise role in mitotic progression remains elusive. To address this issue, the effects of HDAC inhibition were examined upon a variety of mitotic mutants of the fission yeast Schizosaccharomyces pombe, which contains three HDACs that are sensitive to trichostatin A (TSA) and are similar to human HDACs. Here it is shown that HDACs are implicated in sister chromatid cohesion and separation. A mutant of the cohesin loader Mis4 (adherin) was hypersensitive to TSA and synthetically lethal with HDAC deletion mutations. TSA treatment of mis4 mutant cells decreased chromatin-bound cohesins in the chromosome arm region. By contrast, HDAC inhibitors and clr6 HDAC mutations rescued temperature sensitive (ts) phenotypes of the mutants of the ubiquitin ligase complex anaphase-promoting complex/cyclosome (APC/C), which display metaphase arrest. This suppression coincided with facilitated complex formation of APC/C. Moreover, our mass spectrometry analysis showed that an APC/C subunit, Cut23/APC8, is acetylated. HATs and HDACs might directly target adherin and APC/C to ensure proper chromosome segregation, and anti-tumour effects of HDAC inhibitors could be attributed to this deregulation.
Yuu Kimata; Akihisa Matsuyama; Koji Nagao; Kanji Furuya; Chikashi Obuse; Minoru Yoshida; Mitsuhiro Yanagida
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cell science     Volume:  121     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-20     Completed Date:  2008-07-31     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  1107-18     Citation Subset:  IM    
CREST Research Program, Japan Science and Technology Corporation, Graduate School of Biostudies, Kyoto University, Yoshida-Honmachi, Kyoto 606-8501, Japan.
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MeSH Terms
Chromatids / drug effects,  genetics
Chromatin Immunoprecipitation
Fungal Proteins / antagonists & inhibitors,  genetics,  metabolism*
Histone Deacetylase Inhibitors
Histone Deacetylases / genetics,  metabolism*
Hydroxamic Acids / pharmacology
Mass Spectrometry
Mitosis / drug effects,  genetics
Schizosaccharomyces / drug effects,  genetics,  metabolism*
Sister Chromatid Exchange / drug effects
Ubiquitin-Protein Ligase Complexes / drug effects,  genetics,  metabolism*
Reg. No./Substance:
0/Fungal Proteins; 0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 58880-19-6/trichostatin A; EC Deacetylases; EC Ligase Complexes; EC complex

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