Extrachromosomal Circular DNA: Current Knowledge and Implications for CNS Aging and Neurodegeneration

Area of Science:

• Genetics
• Neuroscience
• Molecular Biology

Background:

• Somatic gene copy number alterations impact organ function and aging.
• Post-mitotic neurons in the central nervous system (CNS) accumulate DNA damage over a lifetime.
• DNA damage and repair can generate extrachromosomal circular DNA (eccDNA).

Purpose of the Study:

• To explore the role of extrachromosomal circular DNA in CNS aging and neurodegeneration.
• To summarize current knowledge on eccDNA biogenesis, homeostasis, and gene regulatory impacts.
• To propose a critical function for the 'circulome' in the aging brain.

Main Methods:

• Literature review and synthesis of current knowledge on eccDNA.
• Analysis of eccDNA's potential role in DNA damage and repair mechanisms.
• Comparison of eccDNA functions in tumor tissues and the CNS.

Main Results:

• Extrachromosomal circular DNAs can amplify gene copies and transcripts, creating a dynamic chromatin pool.
• Mosaicism of circular DNAs is implicated in cancer plasticity and drug resistance.
• The 'circulome' is proposed to play a significant role in CNS aging and neurodegeneration.

Conclusions:

• The accumulation and impact of somatic gene copy number alterations on CNS aging remain largely unresolved.
• Extrachromosomal circular DNAs are potential key players in the aging process and age-related neurodegenerative diseases.
• Future research should investigate the specific influence of eccDNA based on sequence complexity, distribution, and cell-type abundance.