MYC assembles and stimulates topoisomerases 1 and 2 in a “topoisome”

Das, Subhendu; Kuzin, Vladislav; Cameron, Donald P.; Sanford, Suzanne; Jha, Rajiv Kumar; Nie, Zhongzhen; Rosello, Marta Trullols; Holewinski, Ronald J.; Andrésson, Þorkell; Wiśniewski, Jan; Natsume, Toyoaki; Price, David H.; Lewis, Brian A.; Kouzine, Fedor; Levens, David; Baranello, Laura

doi:10.1016/j.molcel.2021.11.016

Cited by 49 publications

(45 citation statements)

References 109 publications

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“…This is because TOP1cc formation is suppressed until after pause release when the phosphorylated-RNAPII stimulates TOP1 activity. As MYC affects the levels of TOP1ccs ( Das et al., 2022 ), we observe a reduction in TOP1 activity around the TSSs upon MYC degradation (right). (B) Average TOP1 CAD-seq profile (RPM) at TSSs comparing all expressed genes and the top 30% expressed genes (based on RNA-seq from ( Goldenson et al., 2020 )).…”

Section: Expected Outcomesmentioning

confidence: 89%

Section: Expected Outcomesmentioning

confidence: 89%

“… Note: If you aim to detect TOP2ccs, after IP with anti-TOP2 antibody and DNA purification, an additional step of Exonuclease VII (NEB, M0379S) treatment and purification is required for removing the covalently bound tyrosyl residue which can block both 5′ ends of DNA and completely prevent adapter ligation and amplification during library preparation ( Das et al., 2022 ). Based on the Qubit DNA quantifications (step 49) take equal DNA amounts of each sample and transfer to 200 μL PCR tubes.…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

“…Compared to other approaches for the genomic study of topoisomerases, TOP1 CAD-seq provides information about active TOP1 engaged on the DNA, taking advantage of low background due to absence of crosslinking. For complete details on the use and execution of this protocol, please refer to Das et al. (2022) .…”

mentioning

confidence: 99%

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TOP1 CAD-seq: A protocol to map catalytically engaged topoisomerase 1 in human cells

Kuzin¹,

Wiegard²,

Cameron³

et al. 2022

STAR Protocols

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Section: Expected Outcomesmentioning

confidence: 89%

Section: Expected Outcomesmentioning

confidence: 89%

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

TOP1 CAD-seq: A protocol to map catalytically engaged topoisomerase 1 in human cells

Kuzin¹,

Wiegard²,

Cameron³

et al. 2022

STAR Protocols

Self Cite

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“…One possibility is that when TOP3B binds an mRNA, it may not necessarily catalyze topological reactions on this mRNA. It is known that for TOP1 and TOP2, their DNA targets identified by ChIP-seq are often different from those identified by methods that are based on capturing the intermediate of topoisomerase reactions--DNA-topoisomerase cleavage complex (52)(53)(54)(55)(56)(57). The targets identified by the latter methods more actually represent the genes that are catalytically regulated by the topoisomerases.…”

Section: Top3b Preferentially Binds Long Mrnas and Enhance Their Leve...mentioning

confidence: 99%

A dual-activity topoisomerase complex regulates translation and abundance of mRNAs important for psychiatric disorders

Xue²,

Sharov

et al. 2022

Preprint

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Topoisomerase 3b (TOP3B)-TDRD3 is a dual-activity topoisomerase complex in animals that can change topology for both DNA and RNA. A current hypothesis proposes that this complex interacts with Fragile X mental retardation protein, FMRP, to regulate mRNA translation. Here we examined this hypothesis by identifying TOP3B-TDRD3-bound mRNAs in human HCT116 cells; and analyzing the effect of inactivating TOP3B, TOP3B catalytic activity, TDRD3, and FMRP, on translation and abundance of these mRNAs. We found that TOP3B-TDRD3 resembles FMRP in preferentially binding to coding regions of long mRNAs. Complete inactivation of TOP3B protein, but not a point mutation that only disrupts TOP3B catalytic activity, preferentially reduced the abundance of the TOP3B-TDRD3-bound mRNAs. Moreover, ablation of the complex or inactivation of TOP3B catalytic activity alters translation for some but not all TOP3B-TDRD3 bound mRNAs, suggesting that TOP3B-TDRD3 may solve topological problems for specific mRNAs. Finally, several schizophrenia and autism-risk genes are bound and regulated by TOP3B-TDRD3 in mRNA translation and abundance by topoisomerase activity dependent and independent manners. Our data suggest that TOP3B-TDRD3 can regulate mRNA translation and abundance by topoisomerase activity dependent or independent mechanisms; and disruption of this function could contribute to pathogenesis of psychiatric disorders in TOP3B mutation carriers.

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Immune evasion: An imperative and consequence of MYC deregulation

Krenz,

Lee,

Kannan

et al. 2024

Molecular Oncology

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MYC has been implicated in the pathogenesis of a wide range of human tumors and has been described for many years as a transcription factor that regulates genes with pleiotropic functions to promote tumorigenic growth. However, despite extensive efforts to identify specific target genes of MYC that alone could be responsible for promoting tumorigenesis, the field is yet to reach a consensus whether this is the crucial function of MYC. Recent work shifts the view on MYC's function from being a gene‐specific transcription factor to an essential stress resilience factor. In highly proliferating cells, MYC preserves cell integrity by promoting DNA repair at core promoters, protecting stalled replication forks, and/or preventing transcription‐replication conflicts. Furthermore, an increasing body of evidence demonstrates that MYC not only promotes tumorigenesis by driving cell‐autonomous growth, but also enables tumors to evade the host's immune system. In this review, we summarize our current understanding of how MYC impairs antitumor immunity and why this function is evolutionarily hard‐wired to the biology of the MYC protein family. We show why the cell‐autonomous and immune evasive functions of MYC are mutually dependent and discuss ways to target MYC proteins in cancer therapy.

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MYC assembles and stimulates topoisomerases 1 and 2 in a “topoisome”

Cited by 49 publications

References 109 publications

TOP1 CAD-seq: A protocol to map catalytically engaged topoisomerase 1 in human cells

TOP1 CAD-seq: A protocol to map catalytically engaged topoisomerase 1 in human cells

A dual-activity topoisomerase complex regulates translation and abundance of mRNAs important for psychiatric disorders

Immune evasion: An imperative and consequence of MYC deregulation

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