{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:02:54Z","timestamp":1789470174835,"version":"build-2803163510"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Sleep and wake are fundamental brain states that coordinate diverse physiological processes required for long-term health and survival. Recent research in molecular neuroscience and chronobiology has begun to clarify how sleep\u2013wake cycles and circadian timing intersect with genomic maintenance mechanisms in the nervous system. In this Review, we summarize current evidence that sleep and circadian rhythms temporally regulate neuronal genome stability, with a particular focus on how they modulate neuronal retrotransposon activity. We discuss circadian clock-dependent regulation of DNA repair pathways, the contribution of sleep to chromosomal integrity and chromosome dynamics, and emerging data on temporally-dependent retrotransposon activity across the sleep\u2013wake cycle. Taken together, the studies we review suggest that sleep may provide a permissive state during which neurons engage genome-protective processes, including up-regulation of DNA repair factors, changes in chromatin organization, and silencing of retrotransposon activity. We further propose that these mechanisms may be relevant to neurodegenerative disorders, although much of the current evidence linking sleep and circadian disruption to retrotransposon dysregulation, genomic instability, and cognitive decline remains preclinical or correlative in humans.<\/jats:p>","DOI":"10.3389\/fnins.2026.1865440","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:07:47Z","timestamp":1789466867000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sleep and circadian regulation of DNA repair and retrotransposons in neuronal genome stability and neurodegenerative disease mechanisms"],"prefix":"10.3389","volume":"20","author":[{"given":"Abhas","family":"Rajhans","sequence":"first","affiliation":[{"name":"Ketema Paul Lab, University of California Los Angeles, Department of Integrative Biology and Physiology","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella","family":"Kye","sequence":"additional","affiliation":[{"name":"Ketema Paul Lab, University of California Los Angeles, Department of Integrative Biology and Physiology","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vedant","family":"Balu","sequence":"additional","affiliation":[{"name":"Ketema Paul Lab, University of California Los Angeles, Department of Integrative Biology and Physiology","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Glanzman","sequence":"additional","affiliation":[{"name":"David Glanzman Lab, University of California Los Angeles, Department of Integrative Biology and Physiology","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketema N.","family":"Paul","sequence":"additional","affiliation":[{"name":"Ketema Paul Lab, University of California Los Angeles, Department of Integrative Biology and Physiology","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1080\/2159256X.2015.1037416","article-title":"LINE-1 activity as molecular basis for genomic instability associated with light exposure at night","volume":"5","author":"Belancio","year":"2015","journal-title":"Mob. Genet. Elements"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"36804","DOI":"10.1038\/srep36804","article-title":"Contribution of sleep to the repair of neuronal DNA double-strand breaks: evidence from flies and mice","volume":"6","author":"Bellesi","year":"2016","journal-title":"Sci. Rep."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.3109\/07420528.2010.490065","article-title":"Epigenetic effects of shiftwork on blood DNA methylation","volume":"27","author":"Bollati","year":"2010","journal-title":"Chronobiol. Int."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1177\/0748730410395732","article-title":"Circadian clock gene expression in brain regions of Alzheimer\u2019s disease patients and control subjects","volume":"26","author":"Cermakian","year":"2011","journal-title":"J. Biol. Rhythm."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"5847","DOI":"10.3390\/ijms23105847","article-title":"The role of transposable elements of the human genome in neuronal function and pathology","volume":"23","author":"Chesnokova","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"7694","DOI":"10.1093\/nar\/gku503","article-title":"Regulation of L1 expression and retrotransposition by melatonin and its receptor: implications for cancer risk associated with light exposure at night","volume":"42","author":"de Haro","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/ng.368","article-title":"Regulated retrotransposon transcriptome of mammalian cells","volume":"41","author":"Faulkner","year":"2009","journal-title":"Nat. Genet."},{"key":"ref9002","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/978-3-031-59286-7_12","article-title":"Potential contribution of retrotransposons to learning and memory","volume-title":"Epigenetics in biological communication","author":"Glanzman","year":"2024"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s13024-021-00504-w","article-title":"Sleep and circadian rhythms in Parkinson\u2019s disease and preclinical models","volume":"17","author":"Hunt","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"zsz121","DOI":"10.1093\/sleep\/zsz121","article-title":"Sleep duration and fragmentation in relation to leukocyte DNA methylation in adolescents","volume":"42","author":"Jansen","year":"2019","journal-title":"Sleep"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1186\/s13059-021-02409-9","article-title":"Evolution of mouse circadian enhancers from transposable elements","volume":"22","author":"Judd","year":"2021","journal-title":"Genome Biol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"4427","DOI":"10.1093\/nar\/gku094","article-title":"Modulation of ATR-mediated DNA damage checkpoint response by cryptochrome 1","volume":"42","author":"Kang","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1101\/gad.1640708","article-title":"DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes","volume":"22","author":"Kuramochi-Miyagawa","year":"2008","journal-title":"Genes Dev."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.tins.2013.05.004","article-title":"New mechanisms in memory storage: piRNAs and epigenetics","volume":"36","author":"Landry","year":"2013","journal-title":"Trends Neurosci."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"89023","DOI":"10.7554\/eLife.89023","article-title":"Modulation of RNA processing genes during sleep-dependent memory","volume":"12","author":"Li","year":"2024","journal-title":"eLife"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"3323","DOI":"10.1093\/nar\/gkac146","article-title":"BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates","volume":"50","author":"Liang","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref9001","doi-asserted-by":"publisher","first-page":"4980","DOI":"10.1016\/j.cell.2025.06.031","article-title":"Single-cell multiregion epigenomic rewiring in Alzheimer\u2019s disease progression and cognitive resilience","volume":"188","author":"Liu","year":"2025","journal-title":"Cell"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1620343","DOI":"10.3389\/fimmu.2025.1620343","article-title":"Microglial clock dysfunction during neuroinflammation impairs oligodendrocyte progenitor cell recruitment and disrupts neuroimmune homeostasis","volume":"16","author":"Lu","year":"2025","journal-title":"Front. 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Neuropsiquiatr."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1038\/nrg.2016.150","article-title":"Transcriptional architecture of mammalian circadian clocks","volume":"18","author":"Takahashi","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"7095","DOI":"10.1038\/s41467-023-42751-z","article-title":"Spatial transcriptomics reveals unique gene expression changes in different brain regions after sleep deprivation","volume":"14","author":"Vanrobaeys","year":"2023","journal-title":"Nat. Commun."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"6514","DOI":"10.4081\/eb.2017.6514","article-title":"Potential impact of primate-specific SVA retrotransposons during the evolution of human cognitive function","volume":"6","author":"Vasieva","year":"2017","journal-title":"Trends Evol. 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