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An Acetyl-Click Chemistry Assay to Measure Histone Acetyltransferase 1 Acetylation
Published on: January 26, 2024
The ATAC acetyl transferase complex controls mitotic progression by targeting non-histone substrates
Meritxell Orpinell1, Marjorie Fournier, Anne Riss
1Department of Functional Genomics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, INSERM U964, Université de Strasbourg, Illkirch Cedex, France.
The EMBO Journal
|June 22, 2010
Summary
The Ada Two A containing (ATAC) complex regulates cell division by acetylating Cyclin A, targeting it for degradation. This process is crucial for proper mitotic progression and cell cycle control.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Chromatin compaction is essential for DNA processes, with maximal condensation occurring during mitosis.
- Histone modifications, particularly deacetylation, are linked to mitotic transition and transcriptional repression.
Purpose of the Study:
- To investigate the role of the Ada Two A containing (ATAC) complex in mitotic progression.
- To elucidate the mechanism by which ATAC regulates cell cycle progression.
Main Methods:
- RNA interference (RNAi) to deplete ATAC subunits (Ada2a/Ada3).
- Analysis of cell cycle progression (M/G1 transition).
- Assessment of cell division defects (centrosome multiplication, spindle/midbody formation, binucleation).
- Immunofluorescence to detect ATAC localization and protein acetylation (histone H4K16, alpha-tubulin).
- Investigation of direct ATAC targets, including Cyclin A/Cdk2.
Main Results:
- Depletion of ATAC subunits caused delayed M/G1 transition and significant cell division defects.
- ATAC was found to localize to the mitotic spindle.
- ATAC directly acetylates Cyclin A/Cdk2, promoting Cyclin A degradation.
- This acetylation-mediated degradation of Cyclin A impacts SIRT2 deacetylase activity.
Conclusions:
- The ATAC complex plays a critical role in regulating mitotic progression.
- ATAC controls cell cycle progression via direct acetylation of non-histone targets, specifically Cyclin A.
- This newly identified pathway highlights ATAC's function in managing Cyclin A activity for proper cell division.
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