IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-03393-8.html
   My bibliography  Save this article

MRN complex-dependent recruitment of ubiquitylated BLM helicase to DSBs negatively regulates DNA repair pathways

Author

Listed:
  • Vivek Tripathi

    (National Institute of Immunology)

  • Himanshi Agarwal

    (National Institute of Immunology)

  • Swati Priya

    (National Institute of Immunology)

  • Harish Batra

    (National Institute of Immunology)

  • Priyanka Modi

    (National Institute of Immunology)

  • Monica Pandey

    (Indian Institute of Science)

  • Dhurjhoti Saha

    (Institute of Genomics and Integrative Biology, CSIR)

  • Sathees C. Raghavan

    (Indian Institute of Science)

  • Sagar Sengupta

    (National Institute of Immunology)

Abstract

Mutations in BLM in Bloom Syndrome patients predispose them to multiple types of cancers. Here we report that BLM is recruited in a biphasic manner to annotated DSBs. BLM recruitment is dependent on the presence of NBS1, MRE11 and ATM. While ATM activity is essential for BLM recruitment in early phase, it is dispensable in late phase when MRE11 exonuclease activity and RNF8-mediated ubiquitylation of BLM are the key determinants. Interaction between polyubiquitylated BLM and NBS1 is essential for the helicase to be retained at the DSBs. The helicase activity of BLM is required for the recruitment of HR and c-NHEJ factors onto the chromatin in S- and G1-phase, respectively. During the repair phase, BLM inhibits HR in S-phase and c-NHEJ in G1-phase. Consequently, inhibition of helicase activity of BLM enhances the rate of DNA alterations. Thus BLM utilizes its pro- and anti-repair functions to maintain genome stability.

Suggested Citation

  • Vivek Tripathi & Himanshi Agarwal & Swati Priya & Harish Batra & Priyanka Modi & Monica Pandey & Dhurjhoti Saha & Sathees C. Raghavan & Sagar Sengupta, 2018. "MRN complex-dependent recruitment of ubiquitylated BLM helicase to DSBs negatively regulates DNA repair pathways," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03393-8
    DOI: 10.1038/s41467-018-03393-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-03393-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-03393-8?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Yun-Long Wang & Wan-Wen Zhao & Shao-Mei Bai & Li-Li Feng & Shu-Ying Bie & Li Gong & Fang Wang & Ming-Biao Wei & Wei-Xing Feng & Xiao-Lin Pang & Cao-Litao Qin & Xin-Ke Yin & Ying-Nai Wang & Weihua Zhou, 2022. "MRNIP condensates promote DNA double-strand break sensing and end resection," Nature Communications, Nature, vol. 13(1), pages 1-16, 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:9:y:2018:i:1:d:10.1038_s41467-018-03393-8. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.