Journal article
MYC assembles and stimulates topoisomerases 1 and 2 in a “topoisome”
Molecular cell, Vol.82(1), pp.140-158.e12
01/06/2022
DOI: 10.1016/j.molcel.2021.11.016
PMCID: PMC8750365
PMID: 34890565
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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•MYC manages high levels of torsional stress during transcription and replication•Both topoisomerase 1 and 2 activities are stimulated by MYC inside cells•The MYC nucleated “topoisome” harbors TOP1 and TOP2 and is activated at promoters•Inclusion of TOP2A versus TOP2B in a topoisome is decided by MYC versus MYCN, respectively
Using biochemical and genomic approaches, Das et al. demonstrate that MYC or MYCN each unite TOP1 with TOP2A or TOP2B, respectively, in a “topoisome” in which their enzymatic activities are stimulated to resolve the local and global DNA topological issues associated with high output transcription.
Details
- Title: Subtitle
- MYC assembles and stimulates topoisomerases 1 and 2 in a “topoisome”
- Creators
- Subhendu K. Das - National Cancer InstituteVladislav Kuzin - Karolinska InstitutetDonald P. Cameron - Karolinska InstitutetSuzanne Sanford - National Cancer InstituteRajiv Kumar Jha - National Cancer InstituteZuqin Nie - National Cancer InstituteMarta Trullols Rosello - Karolinska InstitutetRonald Holewinski - Leidos Biomedical Research Inc. (United States)Thorkell Andresson - Leidos Biomedical Research Inc. (United States)Jan Wisniewski - Confocal Microscopy and Digital Imaging Facility, National Cancer Institute, Bethesda, MD 20892, USAToyoaki Natsume - National Institute of GeneticsDavid H. Price - University of IowaBrian A. Lewis - National Cancer InstituteFedor Kouzine - National Cancer InstituteDavid Levens - National Cancer InstituteLaura Baranello - Karolinska Institutet
- Resource Type
- Journal article
- Publication Details
- Molecular cell, Vol.82(1), pp.140-158.e12
- DOI
- 10.1016/j.molcel.2021.11.016
- PMID
- 34890565
- PMCID
- PMC8750365
- NLM abbreviation
- Mol Cell
- ISSN
- 1097-2765
- eISSN
- 1097-4164
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 01/06/2022
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9984293078102771
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