AURORA A interacts with DICER and SETD2 to promote S-phase progression
Juliane Müller1,2, Tina Daunke1, Nicola Berner3
1Institute of Biochemistry, University of Kiel, 24118, Kiel, Germany.
EMBO Reports
|July 1, 2026
Summary
Aurora A kinase has a newly discovered scaffolding role in S-phase, interacting with RNA-binding proteins like DICER to resolve DNA replication stress and prevent spurious transcription.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Aurora A kinase is crucial for cell division (mitotic progression).
- Catalytic inhibition of Aurora A halts cells at the G2/M transition.
- PROTACs targeting Aurora A revealed a non-catalytic scaffolding function in S-phase.
Purpose of the Study:
- To investigate the non-catalytic scaffolding function of Aurora A during S-phase.
- To identify and characterize the S-phase interactome of Aurora A.
- To elucidate the mechanism of Aurora A's role in resolving replicative stress.
Main Methods:
- Proteolysis targeting chimeras (PROTACs) for Aurora A degradation.
- S-phase interactome profiling.
- Biochemical fractionation and gradient analysis.
- Chromatin association studies.
Main Results:
- Aurora A interacts with RNA-binding proteins, including DICER, forming nuclear complexes.
- RNA degradation influences the complex's localization.
- Aurora A depletion affects SETD2's chromatin association and localization.
- A dual-output model for the S-phase Aurora A complex was proposed.
Conclusions:
- Aurora A possesses a non-catalytic scaffolding function essential for S-phase progression.
- The S-phase Aurora A complex recruits RNA-binding proteins to R-loops for processing.
- Aurora A facilitates replicative stress resolution by recruiting SETD2 to prevent spurious transcription.
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