The DOI matches its Crossref record; 84 of the 84 references it cites were found in a registry or an index.
Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons
Open accessAbstract
Neurons are the longest-lived cells in our bodies and lack DNA replication, which makes them reliant on a limited repertoire of DNA repair mechanisms to maintain genome fidelity. These repair mechanisms decline with age, but we have limited knowledge of how genome instability emerges and what strategies neurons and other long-lived cells may have evolved to protect their genomes over the human life span. A targeted sequencing approach in human embryonic stem cell-induced neurons shows that, in neurons, DNA repair is enriched at well-defined hotspots that protect essential genes. These hotspots are enriched with histone H2A isoforms and RNA binding proteins and are associated with evolutionarily conserved elements of the human genome. These findings provide a basis for understanding genome integrity as it relates to aging and disease in the nervous system.
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In the citing paper
“This process promotes extensive endogenous DNA damage in neuronal enhancers, safeguards cell identities but could also lead to base mutations12–15.”
From Single-cell parallel analysis of DNA damage and transcriptome reveals selective genome vulnerability (2025) · cites this paper as [13]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This process promotes extensive endogenous DNA damage in neuronal enhancers, safeguards cell identities but could also lead to base mutations12–15.”
From Single-cell parallel analysis of DNA damage and transcriptome reveals selective genome vulnerability (2025) · cites this paper as [13]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This process promotes extensive endogenous DNA damage in neuronal enhancers, safeguards cell identities but could also lead to base mutations12–15.”
From Single-cell parallel analysis of DNA damage and transcriptome reveals selective genome vulnerability (2025) · cites this paper as [13]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Recent studies revealed that DNA repair hotspots are enriched in a subset of regulatory regions including enhancers, to protect the identities and functions of postmitotic cells (such as neurons)12,13,15.”
From Single-cell parallel analysis of DNA damage and transcriptome reveals selective genome vulnerability (2025) · cites this paper as [13]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Moreover, the observed DNA damage hotspots are combined results from DNA damage formation and repair12,13.”
From Single-cell parallel analysis of DNA damage and transcriptome reveals selective genome vulnerability (2025) · cites this paper as [13]
Experimental — accuracy not yet measured
In the citing paper
“neurons also actively induce both DSBs and single-stranded breaks as part of their normal physiology”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [10]
In the citing paper
“we are just beginning to appreciate the significance of a lesion’s genomic location in relation to its effect on neuronal activity and, ultimately, degeneration”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Reid et al, 2021
In the citing paper
“DNA repair mapping reveals that postmitotic neurons do indeed accumulate breaks in regulatory elements associated with neuronal function”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Reid et al, 2021
In the citing paper
“To this end, genome‐wide profiling of DNA breaks in post‐mitotic neurons have revealed that their locations are likely major mediators of their toxicity.”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Reid et al, 2021
In the citing paper
“As described earlier, the use of nucleoside analog incorporation to map DNA repair has led to the observation that postmitotic neurons harbor SSBs and other forms of breaks in the regulatory regions of genes that modulate synaptic plasticity and neuronal function (Reid et al, 2021; Wu et al, 2021).”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Reid et al, 2021
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Metadata
- Authors
- Reid, D. A., Reed, P. J., Schlachetzki, J. C. M., Nitulescu, I. I., Chou, G., Tsui, E. C., Jones, J. R., Chandran, S., Lu, A. T., McClain, C. A., Ooi, J. H., Wang, T.-W., Lana, A. J., Linker, S. B., Ricciardulli, A. S., Lau, S., Schafer, S. T., Horvath, S., Dixon, J. R., Hah, N., Glass, C. K., & Gage, F. H.
- Affiliations
- Salk Institute for Biological Studies (US)
- University of California San Diego (US)
- University of California, Los Angeles (US)
- Corresponding author
- Reid, Dylan A.
- Reed, Patrick J.
- Schlachetzki, Johannes C. M.
- Nitulescu, Ioana I.
- Chou, Grace
- Tsui, Enoch C.
- Jones, Jeffrey R.
- Gage, Fred H.
- ORCID
- Reid, Dylan A.
- Reed, Patrick J.
- Schlachetzki, Johannes C. M.
- Nitulescu, Ioana I.
- Chou, Grace
- Tsui, Enoch C.
- Jones, Jeffrey R.
- Chandran, Sahaana
- Lu, Ake T.
- McClain, Claire A.
- Ooi, Jean H.
- Wang, Tzu-Wen
- Lana, Addison J.
- Linker, Sara B.
- Ricciardulli, Anthony S.
- Lau, Shong
- Schafer, Simon T.
- Horvath, Steve
- Dixon, Jesse R.
- Hah, Nasun
- Glass, Christopher K.
- Gage, Fred H.
- Venue
- Science
- Published
- 2021-04-02
- Volume
- 372
- Issue
- 6537
- Pages
- 91-94
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC9179101
- OpenAlex
- W3151212872
- Cited by
- 121
- References
- 81
- Citations by year
- 2026: 18 · 2025: 19 · 2024: 24 · 2023: 26 · 2022: 27 · 2021: 7
- FWCI
- 6.59
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH Office of the Director (AG056306, DP5OD023071-03)
- Alzheimer’s Association (AARF-17-504089)
- Leona M. and Harry B. Helmsley Charitable Trust
- JPB Foundation
- NIH (R01AG056411-02)
- American Heart Association/Paul G. Allen Frontiers Group Brain Health & Cognitive Impairment Initiative (19PABHI34610000)
- Dolby Charitable Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- DNA repair, genomic instability, postmitotic neurons, RNA-binding proteins, embryonic stem cell-derived neurons, aging, genome stability, essential genes
- MeSH terms
- Aging, Deoxyuridine, DNA Damage, DNA Repair, Histones, Humans, Mitosis, Mutation, Nervous System Diseases, Neurons, Promoter Regions, Genetic, Transcription, Genetic, Genome, Human, RNA-Binding Proteins, Sequence Analysis, DNA, DNA, Intergenic, Genomic Instability, Embryonic Stem Cells
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