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Reciprocal interaction between SIRT6 and APC/C regulates genomic stability
Helin Wang1, Kangze Feng1, Qingtao Wang2
1MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
Scientific Reports
|July 10, 2021
Summary
SIRT6 overexpression causes mitosis errors and aneuploidy. SIRT6 and the anaphase-promoting complex/cyclosome (APC/C) have a reciprocal regulatory relationship impacting genome stability.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- SIRT6 is an NAD+-dependent deacetylase crucial for maintaining genome stability and accurate mitosis.
- Dysregulation of SIRT6 is linked to genomic instability and aneuploidy.
Purpose of the Study:
- To investigate the role of SIRT6 in mitosis fidelity.
- To elucidate the regulatory relationship between SIRT6 and the anaphase-promoting complex/cyclosome (APC/C).
Main Methods:
- Overexpression of SIRT6 in cells.
- Identification of SIRT6 as an APC/C substrate.
- Analysis of ubiquitination-proteasome pathway involvement.
- Deacetylation assays to study SIRT6-CDH1 interaction.
Main Results:
- SIRT6 overexpression induced mitosis defects and aneuploidy.
- SIRT6 is a substrate of APC/C, degraded via ubiquitination.
- SIRT6 deacetylated and promoted the degradation of CDH1, an APC/C co-activator.
- This reciprocal regulation led to increased APC/C-CDH1 substrates, centrosome amplification, and chromosome instability.
Conclusions:
- SIRT6 plays a critical role in maintaining genome integrity during mitosis.
- A novel feedback loop exists between SIRT6 and APC/C, essential for proper mitotic progression.
- This interaction highlights a new mechanism contributing to chromosome instability.
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