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Published on: August 2, 2024
Epigenetic orchestration of the DNA damage response: Insights into the regulatory mechanisms
Atanu Mondal1, Agniswar Sarkar2, Dipanwita Das3
1Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, India; Homi Bhabha National Institute, Mumbai, India.
Abstract:
The DNA damage response (DDR) is a critical cellular mechanism that safeguards genome integrity and prevents the accumulation of harmful DNA lesions. Increasing evidence highlights the intersection between DDR signaling and epigenetic regulation, offering profound insights into various aspects of cellular function including oncogenesis. This comprehensive review explores the intricate relationship between the epigenetic modifications and DDR activation, with a specific focus on the impact of viral infections. Oncogenic viruses, such as human papillomavirus, hepatitis virus (HBV or HCV), and Epstein-Barr virus have been shown to activate the DDR. Consequently, these DNA damage events trigger a cascade of epigenetic alterations, including changes in DNA methylation patterns, histone modifications and the expression of noncoding RNAs. These epigenetic changes exert profound effects on chromatin structure, gene expression, and maintenance of genome stability. Importantly, elucidation of the viral-induced epigenetic alterations in the context of DDR holds significant implications for comprehending the complexity of cancer and provides potential targets for therapeutic interventions.
Insights
Viral infections activate the DNA damage response (DDR), leading to epigenetic changes that impact genome stability and cancer development. Understanding these DDR-epigenetic links offers potential therapeutic targets.
Area of Science:
- Molecular Biology
- Epigenetics
- Virology
Background:
- The DNA damage response (DDR) is crucial for maintaining genome integrity.
- Epigenetic regulation plays a significant role in cellular functions, including oncogenesis.
- The interplay between DDR and epigenetics is increasingly recognized.
Purpose of the Study:
- To review the intricate relationship between epigenetic modifications and DDR activation.
- To focus on the impact of viral infections on this interplay.
- To explore therapeutic implications.
Main Methods:
- Comprehensive literature review.
- Analysis of existing research on DDR, epigenetics, and viral oncogenesis.
- Synthesis of findings on viral-induced epigenetic alterations.
Main Results:
- Oncogenic viruses (e.g., HPV, HBV, HCV, EBV) activate the DDR.
- Viral-induced DNA damage triggers epigenetic alterations: DNA methylation, histone modifications, noncoding RNA expression.
- These epigenetic changes affect chromatin structure, gene expression, and genome stability.
Conclusions:
- Viral infections induce epigenetic alterations via DDR activation.
- These alterations contribute to cancer development and progression.
- Elucidating these mechanisms provides potential therapeutic targets for cancer treatment.
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