IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-41623-w.html
   My bibliography  Save this article

SENP6 regulates localization and nuclear condensation of DNA damage response proteins by group deSUMOylation

Author

Listed:
  • Laura A. Claessens

    (Leiden University Medical Centre)

  • Matty Verlaan-de Vries

    (Leiden University Medical Centre)

  • Ilona J. Graaf

    (Leiden University Medical Centre)

  • Alfred C. O. Vertegaal

    (Leiden University Medical Centre)

Abstract

The SUMO protease SENP6 maintains genomic stability, but mechanistic understanding of this process remains limited. We find that SENP6 deconjugates SUMO2/3 polymers on a group of DNA damage response proteins, including BRCA1-BARD1, 53BP1, BLM and ERCC1-XPF. SENP6 maintains these proteins in a hypo-SUMOylated state under unstressed conditions and counteracts their polySUMOylation after hydroxyurea-induced stress. Co-depletion of RNF4 leads to a further increase in SUMOylation of BRCA1, BARD1 and BLM, suggesting that SENP6 antagonizes targeting of these proteins by RNF4. Functionally, depletion of SENP6 results in uncoordinated recruitment and persistence of SUMO2/3 at UVA laser and ionizing radiation induced DNA damage sites. Additionally, SUMO2/3 and DNA damage response proteins accumulate in nuclear bodies, in a PML-independent manner driven by multivalent SUMO-SIM interactions. These data illustrate coordinated regulation of SUMOylated DNA damage response proteins by SENP6, governing their timely localization at DNA damage sites and nuclear condensation state.

Suggested Citation

  • Laura A. Claessens & Matty Verlaan-de Vries & Ilona J. Graaf & Alfred C. O. Vertegaal, 2023. "SENP6 regulates localization and nuclear condensation of DNA damage response proteins by group deSUMOylation," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41623-w
    DOI: 10.1038/s41467-023-41623-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-41623-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-41623-w?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. Yaron Galanty & Rimma Belotserkovskaya & Julia Coates & Sophie Polo & Kyle M. Miller & Stephen P. Jackson, 2009. "Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks," Nature, Nature, vol. 462(7275), pages 935-939, December.
    2. Markus Schick & Le Zhang & Sabine Maurer & Hans Carlo Maurer & Konstandina Isaakaidis & Lara Schneider & Upayan Patra & Kathrin Schunck & Elena Rohleder & Julia Hofstetter & Apoorva Baluapuri & Anna K, 2022. "Genetic alterations of the SUMO isopeptidase SENP6 drive lymphomagenesis and genetic instability in diffuse large B-cell lymphoma," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Frauke Liebelt & Nicolette S. Jansen & Sumit Kumar & Ekaterina Gracheva & Laura A. Claessens & Matty Verlaan-de Vries & Edwin Willemstein & Alfred C. O. Vertegaal, 2019. "The poly-SUMO2/3 protease SENP6 enables assembly of the constitutive centromere-associated network by group deSUMOylation," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    4. Ramesh Kumar & Román González-Prieto & Zhenyu Xiao & Matty Verlaan-de Vries & Alfred C. O. Vertegaal, 2017. "The STUbL RNF4 regulates protein group SUMOylation by targeting the SUMO conjugation machinery," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
    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. Jenny Kaur Singh & Rebecca Smith & Magdalena B. Rother & Anton J. L. Groot & Wouter W. Wiegant & Kees Vreeken & Ostiane D’Augustin & Robbert Q. Kim & Haibin Qian & Przemek M. Krawczyk & Román González, 2021. "Zinc finger protein ZNF384 is an adaptor of Ku to DNA during classical non-homologous end-joining," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    2. Orhi Barroso-Gomila & Fredrik Trulsson & Veronica Muratore & Iñigo Canosa & Laura Merino-Cacho & Ana Rosa Cortazar & Coralia Pérez & Mikel Azkargorta & Ibon Iloro & Arkaitz Carracedo & Ana M. Aransay , 2021. "Identification of proximal SUMO-dependent interactors using SUMO-ID," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    3. Orhi Barroso-Gomila & Laura Merino-Cacho & Veronica Muratore & Coralia Perez & Vincenzo Taibi & Elena Maspero & Mikel Azkargorta & Ibon Iloro & Fredrik Trulsson & Alfred C. O. Vertegaal & Ugo Mayor & , 2023. "BioE3 identifies specific substrates of ubiquitin E3 ligases," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    4. Yejinpeng Wang & Lingao Ju & Gang Wang & Kaiyu Qian & Wan Jin & Mingxing Li & Jingtian Yu & Yiliang Shi & Yongzhi Wang & Yi Zhang & Yu Xiao & Xinghuan Wang, 2023. "DNA polymerase POLD1 promotes proliferation and metastasis of bladder cancer by stabilizing MYC," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Joana S. Rodrigues & Miguel Chenlo & Susana B. Bravo & Sihara Perez-Romero & Maria Suarez-Fariña & Tomas Sobrino & Rebeca Sanz-Pamplona & Román González-Prieto & Manuel Narciso Blanco Freire & Ruben N, 2024. "dsRNAi-mediated silencing of PIAS2beta specifically kills anaplastic carcinomas by mitotic catastrophe," Nature Communications, Nature, vol. 15(1), pages 1-30, December.
    6. Sarah Tessier & Omar Ferhi & Marie-Claude Geoffroy & Román González-Prieto & Antoine Canat & Samuel Quentin & Marika Pla & Michiko Niwa-Kawakita & Pierre Bercier & Domitille Rérolle & Marilyn Tirard &, 2022. "Exploration of nuclear body-enhanced sumoylation reveals that PML represses 2-cell features of embryonic stem cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    7. Zeliha Yalçin & Shiu Yeung Lam & Marieke H. Peuscher & Jaco Torre & Sha Zhu & Prasanna V. Iyengar & Daniel Salas-Lloret & Inge Krijger & Nathalie Moatti & Ruben Lugt & Mattia Falcone & Aurora Cerutti , 2024. "UBE2D3 facilitates NHEJ by orchestrating ATM signalling through multi-level control of RNF168," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    8. Fredrik Trulsson & Vyacheslav Akimov & Mihaela Robu & Nila Overbeek & David Aureliano Pérez Berrocal & Rashmi G. Shah & Jürgen Cox & Girish M. Shah & Blagoy Blagoev & Alfred C. O. Vertegaal, 2022. "Deubiquitinating enzymes and the proteasome regulate preferential sets of ubiquitin substrates," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    9. Daniel Salas-Lloret & Néstor García-Rodríguez & Emily Soto-Hidalgo & Lourdes González-Vinceiro & Carmen Espejo-Serrano & Lisanne Giebel & María Luisa Mateos-Martín & Arnoud H. Ru & Peter A. Veelen & P, 2024. "BRCA1/BARD1 ubiquitinates PCNA in unperturbed conditions to promote continuous DNA synthesis," Nature Communications, Nature, vol. 15(1), pages 1-14, 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:14:y:2023:i:1:d:10.1038_s41467-023-41623-w. 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.