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Updated: May 29, 2026

Cell Cycle-specific Measurement of γH2AX and Apoptosis After Genotoxic Stress by Flow Cytometry
Published on: September 1, 2019
Genotoxic stress-mediated cell cycle activities for the decision of cellular fate
1Erol Project Development House for the Disorders of Energy Metabolism, Silivri, Istanbul, Turkey. eroladnan@hotmail.com
Abstract:
Genomic integrity maintenance is critical for prevention of a wide variety of adverse cellular effects including apoptosis, cellular senescence, and malignant cell transformation. Coupled with normal replication, the local intracellular and extracellular stresses cause damage to cellular DNA that is recognized and repaired by the DNA damage response (DDR) pathway. p53 induces the transcription of genes that negatively regulate progression of the cell cycle in response to DNA damage, and thus participates in maintaining genome stability. p53 and many other anti-proliferative factors such as TGF beta regulate the expression of different cyclin-dependent kinase inhibitors (CDKIs). Paradoxically, one of the cellular proliferative factors, c-Myc proto-oncogene also controls the expression of these CDKIs and modulates the fate of cell in response to DNA damage. Furthermore, involvement of numerous other proteins in the DDR and crosstalk between them are likely to substantiate the DDR as one of the genome's most extensive signaling networks. Versatile protein kinases in this network affect the decision about four basic cellular fates, which are quiescence, apoptosis, oncogenesis and senescence, in response to DNA damage.
Insights
Maintaining genomic integrity is crucial for preventing cell damage and cancer. The DNA damage response (DDR) pathway, involving p53 and c-Myc, manages cell fate decisions like apoptosis and senescence in response to DNA damage.
Area of Science:
- Cellular biology
- Molecular genetics
- Cancer research
Background:
- Genomic integrity is vital for preventing apoptosis, senescence, and malignant transformation.
- DNA damage from replication and stress is repaired by the DNA damage response (DDR) pathway.
- The DDR pathway is a complex signaling network involving numerous proteins and kinases.
Purpose of the Study:
- To explore the role of p53 and c-Myc in regulating cell cycle progression and fate in response to DNA damage.
- To elucidate the intricate signaling network of the DDR pathway.
- To understand how the DDR pathway influences cellular decisions like quiescence, apoptosis, oncogenesis, and senescence.
Main Methods:
- Analysis of gene transcription regulation by p53 and c-Myc.
- Investigation of cyclin-dependent kinase inhibitor (CDKI) expression.
- Examination of protein kinase involvement in DDR signaling.
Main Results:
- p53 induces genes that inhibit cell cycle progression, aiding genome stability.
- Both p53 and c-Myc modulate CDKI expression, influencing cell fate.
- The DDR pathway integrates signals to determine cellular outcomes such as quiescence, apoptosis, oncogenesis, and senescence.
Conclusions:
- The DDR pathway is an extensive signaling network critical for maintaining genomic stability.
- p53 and c-Myc play key roles in cell cycle regulation and fate determination following DNA damage.
- Understanding the DDR pathway's crosstalk is essential for comprehending cellular responses to DNA damage and preventing diseases like cancer.
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