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Updated: Jan 11, 2026
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
SOX2 phosphorylation during mitosis limits genomic damage
Charles A C Williams1,2, Dounia Djeghloul3, Nicolas Veland3
1Centre for Regenerative Medicine, Institute for Regeneration and Repair, Cancer Research UK Scotland Centre, University of Edinburgh, Edinburgh EH16 4UU, United Kingdom.
Abstract:
Pioneer transcription factors (TFs) such as SOX2 play critical roles in the control of stem cell identity and are dysregulated in many human cancers. For example, SOX2 regulates the self-renewal of neural stem cells (NSCs) and is typically highly expressed in glioblastoma stem cells (GSCs), where it is known to induce an immature NSC-like state. Here, we explored the regulation of SOX2 by phosphorylation during NSC division and identified an unexpected role for excessive SOX2 pioneer activity in driving mitotic damage. We found that SOX2 phosphorylation during mitosis is a key switch that prevents promiscuous chromatin binding across the genome. Without this regulatory control, excessive SOX2 in mitosis triggers chromatin opening, resulting in increased mitotic transit times and increased chromosomal damage. Therefore, elevated levels of SOX2 in cancers may have dual oncogenic roles: inducing stemness during interphase via its well-known transcriptional roles but simultaneously promoting chromosomal disruptions through unconstrained pioneer factor activity.
Insights
SOX2 phosphorylation regulates its binding to DNA during cell division. Uncontrolled SOX2 activity in cancer promotes stemness and chromosomal damage, indicating dual oncogenic roles.
Area of Science:
- Molecular Biology
- Cancer Research
- Stem Cell Biology
Background:
- Pioneer transcription factors (TFs) like SOX2 control stem cell identity.
- SOX2 is crucial for neural stem cell (NSC) self-renewal and is often overexpressed in glioblastoma stem cells (GSCs).
- Dysregulated SOX2 contributes to cancer development and progression.
Purpose of the Study:
- To investigate the role of SOX2 phosphorylation in regulating its activity during NSC division.
- To understand the consequences of excessive SOX2 pioneer activity on mitotic processes.
- To elucidate the dual oncogenic functions of elevated SOX2 in cancer.
Main Methods:
- Studied SOX2 phosphorylation during neural stem cell division.
- Assessed the impact of SOX2 on chromatin binding and mitotic progression.
- Investigated the relationship between SOX2 levels, mitotic damage, and chromosomal integrity.
Main Results:
- SOX2 phosphorylation acts as a critical regulatory switch during mitosis, preventing widespread genomic binding.
- Excessive SOX2 activity in mitosis leads to uncontrolled chromatin opening.
- This unconstrained activity results in prolonged mitotic duration and increased chromosomal damage.
Conclusions:
- SOX2 phosphorylation is essential for maintaining genomic stability during cell division.
- Elevated SOX2 in cancers may promote stemness through transcriptional roles and induce genomic instability via unconstrained pioneer activity.
- This dual mechanism highlights SOX2 as a significant driver of cancer progression and oncogenesis.
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