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DNA Damage Response and Cell Cycle Regulation in Pluripotent Stem Cells
Andy Chun Hang Chen1,2, Qian Peng2, Sze Wan Fong1
1Department of Obstetrics and Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong, China.
Genes
|October 23, 2021
Summary
Pluripotent stem cells (PSCs) maintain genomic stability through DNA repair mechanisms. Key regulators like FOXM1 and SIRT1 are crucial for preserving the integrity of PSCs for therapeutic use.
Area of Science:
- Stem cell biology
- Genomic stability
- DNA damage response
Background:
- Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have therapeutic potential due to their self-renewal and differentiation capabilities.
- ESCs exhibit unique cell cycle regulation and high homologous recombination (HR) protein expression for DNA double-strand break (DSB) repair.
- iPSC generation involves factors causing oxidative stress and DNA damage, highlighting the importance of DNA repair mechanisms for genomic stability.
Purpose of the Study:
- To review the critical links between HR processes and DNA damage response in PSCs.
- To focus on the roles of FOXM1 and SIRT1 in maintaining genomic integrity within pluripotent stem cells.
- To underscore the significance of genomic stability for PSC proliferation, pluripotency, and safe therapeutic applications.
Main Methods:
- Literature review of studies on DNA damage response and repair pathways in pluripotent stem cells.
- Analysis of the roles of key regulators such as FOXM1, SIRT1, and PUMA in PSC genomic stability.
- Examination of the interplay between transcription regulation, cell cycle control (e.g., P53, CDK1), and DNA repair in PSCs.
Main Results:
- PSCs possess distinct DNA repair mechanisms, including HR, essential for maintaining genomic integrity.
- FOXM1 and SIRT1 are identified as crucial regulators of DNA damage response, influencing downstream targets involved in cell cycle regulation.
- Genomic stability is paramount for preventing cancer development and ensuring the safety and efficacy of PSC-based therapies.
Conclusions:
- The DNA repair mechanisms, particularly HR, are fundamental to maintaining genomic stability in PSCs.
- FOXM1 and SIRT1 play pivotal roles in regulating DNA damage response and preserving genomic integrity in pluripotent stem cells.
- Ensuring genomic stability in PSCs is critical for their successful application in cell-based therapies and reducing tumorigenesis risk.
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