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The Anaphase Promoting Complex is Vital for Histone Metabolism in S. cerevisiae
Author(s) -
Turner Emma Louise,
Pisclevich M,
Dash M,
Wong B,
Jones L,
Harkness T
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb47-b
Subject(s) - chromatin , microbiology and biotechnology , histone , chromatin remodeling , biology , mitosis , ubiquitin ligase , histone h4 , histone code , nucleosome , ubiquitin , genetics , dna , gene
Proper chromosome segregation during mitosis is essential for genomic stability. The precursor required for chromosome packaging is chromatin, a repeating unit of 147bp DNA wrapped around the nucleosome core particle, which is a complex of eight histones, two each of H2A, H2B, H3 and H4. Chromatin assembly, the placement of histones onto naked DNA, depends upon the recruitment of acetylated histones to newly synthesized or damaged DNA. Research suggests a ubiquitin‐protein ligase, the Anaphase Promoting Complex (APC), is involved with both recruitment and acetylation of histones. The APC is an essential evolutionarily conserved factor required for mitotic passage. A multisubunit E3 ubiquitin ligase, the APC plays a major role in regulating the cell cycle by targeting proteins that block mitosis for proteasomal degradation. Newly acetylated histones are deposited onto DNA by the chromatin assembly factor CAF‐I. Recent studies in our lab indicate that the APC and CAF‐I cooperate for efficient mitotic chromatin assembly. The APC may also play a role in recruiting histone acetyltransferases (HATs) to the core histones. Preliminary experiments indicate that various HAT single mutant phenotypes are exacerbated by the temperature sensitive apc5 CA mutant. Furthermore we show that histone acetylation decreases in APC mutants, as does APC substrate degradation. We propose that cell proliferation is promoted by HAT activity in an APC‐dependent manner. As unregulated chromatin formation has been linked to a variety of diseases, including cancer, understanding these mechanisms are key to understanding disease onset and progression. This work is funded by the CIHR.