Extrachromosomal Circular DNA: Current Knowledge and Implications for CNS Aging and Neurodegeneration
Still unresolved is the question of how a lifetime accumulation of somatic gene copy number alterations impact organ functionality and aging and age-related pathologies. Such an issue appears particularly relevant in the broadly post-mitotic central nervous system (CNS), where non-replicative neuron...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/7/2477 |
| _version_ | 1797571598621868032 |
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| author | Quratul Ain Christian Schmeer Diane Wengerodt Otto W. Witte Alexandra Kretz |
| author_facet | Quratul Ain Christian Schmeer Diane Wengerodt Otto W. Witte Alexandra Kretz |
| author_sort | Quratul Ain |
| collection | DOAJ |
| description | Still unresolved is the question of how a lifetime accumulation of somatic gene copy number alterations impact organ functionality and aging and age-related pathologies. Such an issue appears particularly relevant in the broadly post-mitotic central nervous system (CNS), where non-replicative neurons are restricted in DNA-repair choices and are prone to accumulate DNA damage, as they remain unreplaced over a lifetime. Both DNA injuries and consecutive DNA-repair strategies are processes that can evoke extrachromosomal circular DNA species, apparently from either part of the genome. Due to their capacity to amplify gene copies and related transcripts, the individual cellular load of extrachromosomal circular DNAs will contribute to a dynamic pool of additional coding and regulatory chromatin elements. Analogous to tumor tissues, where the mosaicism of circular DNAs plays a well-characterized role in oncogene plasticity and drug resistance, we suggest involvement of the “circulome” also in the CNS. Accordingly, we summarize current knowledge on the molecular biogenesis, homeostasis and gene regulatory impacts of circular extrachromosomal DNA and propose, in light of recent discoveries, a critical role in CNS aging and neurodegeneration. Future studies will elucidate the influence of individual extrachromosomal DNA species according to their sequence complexity and regional distribution or cell-type-specific abundance. |
| first_indexed | 2024-03-10T20:43:00Z |
| format | Article |
| id | doaj.art-7c3b758bf24d4b1b93a478ff441bcbcd |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:43:00Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7c3b758bf24d4b1b93a478ff441bcbcd2023-11-19T20:33:49ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01217247710.3390/ijms21072477Extrachromosomal Circular DNA: Current Knowledge and Implications for CNS Aging and NeurodegenerationQuratul Ain0Christian Schmeer1Diane Wengerodt2Otto W. Witte3Alexandra Kretz4Hans-Berger Department of Neurology, Jena University Hospital, 07747 Jena, Thuringia, GermanyHans-Berger Department of Neurology, Jena University Hospital, 07747 Jena, Thuringia, GermanyHans-Berger Department of Neurology, Jena University Hospital, 07747 Jena, Thuringia, GermanyHans-Berger Department of Neurology, Jena University Hospital, 07747 Jena, Thuringia, GermanyHans-Berger Department of Neurology, Jena University Hospital, 07747 Jena, Thuringia, GermanyStill unresolved is the question of how a lifetime accumulation of somatic gene copy number alterations impact organ functionality and aging and age-related pathologies. Such an issue appears particularly relevant in the broadly post-mitotic central nervous system (CNS), where non-replicative neurons are restricted in DNA-repair choices and are prone to accumulate DNA damage, as they remain unreplaced over a lifetime. Both DNA injuries and consecutive DNA-repair strategies are processes that can evoke extrachromosomal circular DNA species, apparently from either part of the genome. Due to their capacity to amplify gene copies and related transcripts, the individual cellular load of extrachromosomal circular DNAs will contribute to a dynamic pool of additional coding and regulatory chromatin elements. Analogous to tumor tissues, where the mosaicism of circular DNAs plays a well-characterized role in oncogene plasticity and drug resistance, we suggest involvement of the “circulome” also in the CNS. Accordingly, we summarize current knowledge on the molecular biogenesis, homeostasis and gene regulatory impacts of circular extrachromosomal DNA and propose, in light of recent discoveries, a critical role in CNS aging and neurodegeneration. Future studies will elucidate the influence of individual extrachromosomal DNA species according to their sequence complexity and regional distribution or cell-type-specific abundance.https://www.mdpi.com/1422-0067/21/7/2477alternative lengthening of telomeres (ALT)CNS agingcopy number variants (CNV)DNA repairextrachromosomal circular DNA (ecc/ecDNA)genomic plasticity |
| spellingShingle | Quratul Ain Christian Schmeer Diane Wengerodt Otto W. Witte Alexandra Kretz Extrachromosomal Circular DNA: Current Knowledge and Implications for CNS Aging and Neurodegeneration International Journal of Molecular Sciences alternative lengthening of telomeres (ALT) CNS aging copy number variants (CNV) DNA repair extrachromosomal circular DNA (ecc/ecDNA) genomic plasticity |
| title | Extrachromosomal Circular DNA: Current Knowledge and Implications for CNS Aging and Neurodegeneration |
| title_full | Extrachromosomal Circular DNA: Current Knowledge and Implications for CNS Aging and Neurodegeneration |
| title_fullStr | Extrachromosomal Circular DNA: Current Knowledge and Implications for CNS Aging and Neurodegeneration |
| title_full_unstemmed | Extrachromosomal Circular DNA: Current Knowledge and Implications for CNS Aging and Neurodegeneration |
| title_short | Extrachromosomal Circular DNA: Current Knowledge and Implications for CNS Aging and Neurodegeneration |
| title_sort | extrachromosomal circular dna current knowledge and implications for cns aging and neurodegeneration |
| topic | alternative lengthening of telomeres (ALT) CNS aging copy number variants (CNV) DNA repair extrachromosomal circular DNA (ecc/ecDNA) genomic plasticity |
| url | https://www.mdpi.com/1422-0067/21/7/2477 |
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