Abstract
The nervous system is vulnerable to genomic instability and mutations in DNA damage response factors lead to numerous developmental and progressive neurological disorders. Despite this, the sources and mechanisms of DNA damage that are most relevant to the development of neuronal dysfunction are poorly understood. The identification of primarily neurological abnormalities in patients with mutations in TDP1 and TDP2 suggest that topoisomerase-mediated DNA damage could be an important underlying source of neuronal dysfunction. Here we review the potential sources of topoisomerase-induced DNA damage in neurons, describe the cellular mechanisms that have evolved to repair such damage, and discuss the importance of these repair mechanisms for preventing neurological disorders.
Highlights
Morgan Crewe and Ram Madabhushi*Departments of Psychiatry, Neuroscience, and Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, United States
Edited by: Bjoern Schwer, University of California, San Francisco, United StatesReviewed by: George A
The probability of double strand breaks (DSBs) at loop anchors positively correlate with TOP2B binding and are associated with translocation breakpoint clusters that are dysregulated in various cancers (Canela et al, 2017, 2019). Together these results suggest that aberrant repair of TOP2B-mediated DNA DSBs could perturb chromatin organization and gene activity patterns, and thereby contribute to neuronal dysfunction (Figure 3C)
Summary
Departments of Psychiatry, Neuroscience, and Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, United States. The nervous system is vulnerable to genomic instability and mutations in DNA damage response factors lead to numerous developmental and progressive neurological disorders. The sources and mechanisms of DNA damage that are most relevant to the development of neuronal dysfunction are poorly understood. The identification of primarily neurological abnormalities in patients with mutations in TDP1 and TDP2 suggest that topoisomerase-mediated DNA damage could be an important underlying source of neuronal dysfunction. We review the potential sources of topoisomerase-induced DNA damage in neurons, describe the cellular mechanisms that have evolved to repair such damage, and discuss the importance of these repair mechanisms for preventing neurological disorders
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
