IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51906-5.html
   My bibliography  Save this article

Base excision repair and double strand break repair cooperate to modulate the formation of unrepaired double strand breaks in mouse brain

Author

Listed:
  • Aris A. Polyzos

    (Lawrence Berkeley National Laboratory)

  • Ana Cheong

    (Harvard T.H. Chan School of Public Health)

  • Jung Hyun Yoo

    (Lawrence Berkeley National Laboratory)

  • Lana Blagec

    (Lawrence Berkeley National Laboratory)

  • Sneh M. Toprani

    (Harvard T.H. Chan School of Public Health)

  • Zachary D. Nagel

    (Harvard T.H. Chan School of Public Health)

  • Cynthia T. McMurray

    (Lawrence Berkeley National Laboratory)

Abstract

We lack the fundamental information needed to understand how DNA damage in the brain is generated and how it is controlled over a lifetime in the absence of replication check points. To address these questions, here, we integrate cell-type and region-specific features of DNA repair activity in the normal brain. The brain has the same repair proteins as other tissues, but normal, canonical repair activity is unequal and is characterized by high base excision repair (BER) and low double strand break repair (DSBR). The natural imbalance creates conditions where single strand breaks (SSBs) can convert to double strand breaks (DSBs) and reversibly switch between states in response to oxidation both in vivo and in vitro. Our data suggest that, in a normal background of repair, SSBs and DSBs are in an equilibrium which is pushed or pulled by metabolic state. Interconversion of SSB to DSBs provides a physiological check point, which would allow the formation of unrepaired DSBs for productive functions, but would also restrict them from exceeding tolerable limits.

Suggested Citation

  • Aris A. Polyzos & Ana Cheong & Jung Hyun Yoo & Lana Blagec & Sneh M. Toprani & Zachary D. Nagel & Cynthia T. McMurray, 2024. "Base excision repair and double strand break repair cooperate to modulate the formation of unrepaired double strand breaks in mouse brain," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51906-5
    DOI: 10.1038/s41467-024-51906-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51906-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-51906-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Patrick L. Collins & Caitlin Purman & Sofia I. Porter & Vincent Nganga & Ankita Saini & Katharina E. Hayer & Greer L. Gurewitz & Barry P. Sleckman & Jeffrey J. Bednarski & Craig H. Bassing & Eugene M., 2020. "DNA double-strand breaks induce H2Ax phosphorylation domains in a contact-dependent manner," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    2. Namrata Kumar & Arjan F. Theil & Vera Roginskaya & Yasmin Ali & Michael Calderon & Simon C. Watkins & Ryan P. Barnes & Patricia L. Opresko & Alex Pines & Hannes Lans & Wim Vermeulen & Bennett Houten, 2022. "Global and transcription-coupled repair of 8-oxoG is initiated by nucleotide excision repair proteins," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Elizabeth A. Pollina & Daniel T. Gilliam & Andrew T. Landau & Cindy Lin & Naomi Pajarillo & Christopher P. Davis & David A. Harmin & Ee-Lynn Yap & Ian R. Vogel & Eric C. Griffith & M. Aurel Nagy & Emi, 2023. "A NPAS4–NuA4 complex couples synaptic activity to DNA repair," Nature, Nature, vol. 614(7949), pages 732-741, February.
    4. Youtao Lu & Jaehee Lee & Jifen Li & Srinivasa Rao Allu & Jinhui Wang & HyunBum Kim & Kevin L. Bullaughey & Stephen A. Fisher & C. Erik Nordgren & Jean G. Rosario & Stewart A. Anderson & Alexandra V. U, 2023. "CHEX-seq detects single-cell genomic single-stranded DNA with catalytical potential," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    5. Qin Li & Jincong Zhou & Shuai Li & Weifeng Zhang & Yingxue Du & Kuan Li & Yingxiang Wang & Qianwen Sun, 2023. "DNA polymerase ε harmonizes topological states and R-loops formation to maintain genome integrity in Arabidopsis," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    6. Wei Wu & Sarah E. Hill & William J. Nathan & Jacob Paiano & Elsa Callen & Dongpeng Wang & Kenta Shinoda & Niek Wietmarschen & Jennifer M. Colón-Mercado & Dali Zong & Raffaella Pace & Han-Yu Shih & Ste, 2021. "Neuronal enhancers are hotspots for DNA single-strand break repair," Nature, Nature, vol. 593(7859), pages 440-444, May.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. BaDoi N. Phan & Madelyn H. Ray & Xiangning Xue & Chen Fu & Robert J. Fenster & Stephen J. Kohut & Jack Bergman & Suzanne N. Haber & Kenneth M. McCullough & Madeline K. Fish & Jill R. Glausier & Qiao S, 2024. "Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Brittany N. Vandenberg & Marian F. Laughery & Cameron Cordero & Dalton Plummer & Debra Mitchell & Jordan Kreyenhagen & Fatimah Albaqshi & Alexander J. Brown & Piotr A. Mieczkowski & John J. Wyrick & S, 2023. "Contributions of replicative and translesion DNA polymerases to mutagenic bypass of canonical and atypical UV photoproducts," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    3. Megha Jhanji & Chintada Nageswara Rao & Jacob C. Massey & Marion C. Hope & Xueyan Zhou & C. Dirk Keene & Tao Ma & Michael D. Wyatt & Jason A. Stewart & Mathew Sajish, 2022. "Cis- and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Ye Cai & Huifen Cao & Fang Wang & Yufei Zhang & Philipp Kapranov, 2022. "Complex genomic patterns of abasic sites in mammalian DNA revealed by a high-resolution SSiNGLe-AP method," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    5. Weifeng Zhang & Zhuo Yang & Wenjie Wang & Qianwen Sun, 2024. "Primase promotes the competition between transcription and replication on the same template strand resulting in DNA damage," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    6. Juan A. Perez-Bermejo & Oghene Efagene & William M. Matern & Jeffrey K. Holden & Shaheen Kabir & Glen M. Chew & Gaia Andreoletti & Eniola Catton & Craig L. Ennis & Angelica Garcia & Trevor L. Gerstenb, 2024. "Functional screening in human HSPCs identifies optimized protein-based enhancers of Homology Directed Repair," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. Simon D. Schwarz & Jianming Xu & Kapila Gunasekera & David Schürmann & Cathrine B. Vågbø & Elena Ferrari & Geir Slupphaug & Michael O. Hottiger & Primo Schär & Roland Steinacher, 2024. "Covalent PARylation of DNA base excision repair proteins regulates DNA demethylation," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    8. Anchel de Jaime-Soguero & Janina Hattemer & Anja Bufe & Alexander Haas & Jeroen Berg & Vincent Batenburg & Biswajit Das & Barbara Marco & Stefania Androulaki & Nicolas Böhly & Jonathan J. M. Landry & , 2024. "Developmental signals control chromosome segregation fidelity during pluripotency and neurogenesis by modulating replicative stress," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    9. Shaqraa Musawi & Lise-Marie Donnio & Zehui Zhao & Charlène Magnani & Phoebe Rassinoux & Olivier Binda & Jianbo Huang & Arnaud Jacquier & Laurent Coudert & Patrick Lomonte & Cécile Martinat & Laurent S, 2023. "Nucleolar reorganization after cellular stress is orchestrated by SMN shuttling between nuclear compartments," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    10. Athanasios Siametis & Kalliopi Stratigi & Despoina Giamaki & Georgia Chatzinikolaou & Alexia Akalestou-Clocher & Evi Goulielmaki & Brian Luke & Björn Schumacher & George A. Garinis, 2024. "Transcription stress at telomeres leads to cytosolic DNA release and paracrine senescence," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    11. Yanbo Wang & W. Taylor Cottle & Haobo Wang & Momcilo Gavrilov & Roger S. Zou & Minh-Tam Pham & Srinivasan Yegnasubramanian & Scott Bailey & Taekjip Ha, 2022. "Achieving single nucleotide sensitivity in direct hybridization genome imaging," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    12. Jianli Tao & Daniel E. Bauer & Roberto Chiarle, 2023. "Assessing and advancing the safety of CRISPR-Cas tools: from DNA to RNA editing," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    13. Jin H. Yang & Hugo B. Brandão & Anders S. Hansen, 2023. "DNA double-strand break end synapsis by DNA loop extrusion," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    14. Dalia Halawani & Yiqun Wang & Aarthi Ramakrishnan & Molly Estill & Xijing He & Li Shen & Roland H. Friedel & Hongyan Zou, 2023. "Circadian clock regulator Bmal1 gates axon regeneration via Tet3 epigenetics in mouse sensory neurons," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51906-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.