Cell
ArticleRapid induction of c-fos transcription reveals quantitative linkage of RNA polymerase II and DNA topoisomerase I enzyme activities
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Transcription-associated DNA breaks and cancer: A matter of DNA topology
2021, International Review of Cell and Molecular BiologyCitation Excerpt :TOP1 efficiently removes DNA supercoiling arising during transcription. Hence, it is required for proper transcription and is found preferentially in actively transcribed genes (Gilmour et al., 1986; Khobta et al., 2006; Kroeger and Rowe, 1992; Stewart et al., 1990; Zhang et al., 1988). To relax DNA, TOP1 forms a transient covalent bond between its catalytic tyrosine (Y723 in human) and the 3′-phosphate DNA end, and generates a DNA SSB.
Identification of early gene expression changes in primary cultured neurons treated with topoisomerase I poisons
2016, Biochemical and Biophysical Research CommunicationsCitation Excerpt :Many of these differentially expressed transcripts are classified as immediate early genes (IEGs) in that their expression is rapidly regulated in response to stimulus or injury [28]. CPT rapidly induces the transcription of IEGs like Fos, Jun and Egr1 in non-neuronal cells [14–16] as well as in neurons (this study). The IEGs Fos and Jun were upregulated in response to DNA damage induced by CPT and likely mediated their downstream effects through activation of ERK and JNK MAP kinases.
Topoisomerase I deficiency causes RNA polymerase II accumulation and increases AID abundance in immunoglobulin variable genes
2015, DNA RepairCitation Excerpt :In fact, it is noteworthy that Top1 cleavage sites are found throughout transcriptionally active genes but not in silent genes [13,14]. Furthermore, inhibition of Top1 by camptothecin decreased Pol II elongation [15,16], and increased Pol II density in actively transcribed genes [17]. Thus, Top1 is an intricate regulator of Pol II function.
Analysis of Active and Inactive X Chromosome Architecture Reveals the Independent Organization of 30 nm and Large-Scale Chromatin Structures
2010, Molecular CellCitation Excerpt :Supercoils are released by the partial uncoiling of nucleosomal DNA, and it has been shown that histone acetylation also has the ability to release negative supercoils (Norton et al., 1989). Some supercoils are absorbed by the chromatin fiber while others are removed by topoisomerases (Stewart et al., 1990) that are part of the polymerase complex. DNaseI sensitivity of the active β-globin locus is rapidly lost following topoisomerase II inhibition by novobiocin (Villeponteau et al., 1984) and treatment with novobiocin can also block the Drosophila Hsp70-induced heat shock response (Han et al., 1985) implying that supercoiling can disrupt chromatin structure.
Repair of Topoisomerase I-Mediated DNA Damage
2006, Progress in Nucleic Acid Research and Molecular BiologyCitation Excerpt :For example, camptothecin causes a strong holdback of the endogenous c‐myc gene at the P2 promoter, whereas it produces minimal effect on an episomal c‐myc gene or on the basal transcription of the Hsp70 and Gadph genes (63). Camptothecin also enhances the expression of a large number of genes, including c‐fos (63–66). Transcription inhibition is primarily due to transcription elongation blocks by trapped Top1 cleavage complexes (Fig. 4C), which is a high probability event considering that Top1 is associated with transcription complexes (12).
Repair of and checkpoint response to topoisomerase I-mediated DNA damage
2003, Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis