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MYC assembles and stimulates topoisomerases 1 and 2 in a "topoisome"

  1. Author:
    Das, Subhendu K.
    Kuzin, Vladislav
    Cameron, Donald P.
    Sanford, Suzanne
    Jha, Rajiv Kumar
    Nie, Zuqin
    Rosello, Marta Trullols
    Holewinski,Ronald
    Andresson,Thorkell
    Wisniewski, Jan
    Natsume, Toyoaki
    Price, David H.
    Lewis, Brian A.
    Kouzine, Fedor
    Levens, David
    Baranello, Laura

  2. Author Address

    NCI, Lab Pathol, Bethesda, MD 20814 USA.Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden.Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Bethesda, MD 21701 USA.NCI, Confocal Microscopy & Digital Imaging Facil, Bethesda, MD 20892 USA.Natl Inst Genet, Dept Chromosome Sci, Mishima, Shizuoka 4118540, Japan.Tokyo Metropolitan Inst Med Sci, Res Ctr Genome & Med Sci, Tokyo 1568506, Japan.Univ Iowa, Dept Biochem, Iowa City, IA 52242 USA.
    1. Year: 2022
    2. Date: Jan 6
  2. Journal: Molecular Cell
  3. Cell Press
    1. 82
    2. 1
    3. Pages: 140-158. e12
  5. Type of Article: Article
  6. ISSN: 1097-2765
  1. Abstract:

    High-intensity transcription and replication supercoil DNA to levels that can impede or halt these processes. As a potent transcription amplifier and replication accelerator, the proto-oncogene MYC must manage this interfering torsional stress. By comparing gene expression with the recruitment of topoisomerases and MYC to promoters, we surmised a direct association of MYC with topoisomerase 1 (TOP1) and TOP2 that was confirmed in vitro and in cells. Beyond recruiting topoisomerases, MYC directly stimulates their activities. We identify a MYC-nucleated "topoisome" complex that unites TOP1 and TOP2 and increases their levels and activities at promoters, gene bodies, and enhancers. Whether TOP2A or TOP2B is included in the topoisome is dictated by the presence of MYC versus MYCN, respectively. Thus, in vitro and in cells, MYC assembles tools that simplify DNA topology and promote genome function under high output conditions.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.molcel.11.016
  3. PMID: 34890565
  4. PMCID: PMC8750365
  5. View record in Web of Science®
  6. WOS: 000742487300002

Library Notes

  1. Open Access Publication
  2. Fiscal Year: FY2021-2022
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