Microinjection of Anti-Topoisomerase I Immunoglobulin G Into Nuclei of Chironomus Tentans Salivary Gland Cells Leads tO Blockage of Transcription Elongation

Egyházi, E.; Durban, Egon

doi:10.1128/mcb.7.12.4308-4316.1987

Cited by 2 publications

(1 citation statement)

References 27 publications

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“…Topo I has been detected at loci of Drosophila polytene chromosomes that are transcriptionally active (25). The rates of pol I and pol II transcription were inhibited when anti-topo I antibody was microinjected into the nuclei of Chironomus tentans salivary gland cells (26), and the topo I inhibitor camptothecin repressed rRNA synthesis (27). Double temperature sensitive mutants of topo I and topo II in yeast grown at the restrictive temperature resulted in the reduction of rRNA, and to a lesser extent mRNA, synthesis (7,10).…”

Section: Discussionmentioning

confidence: 99%

Elongation by RNA polymerase II on chromatin templates requires topoisomerase activity

Mondal

2003

Nucleic Acids Research

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Transcription on chromatin by RNA polymerase II (pol II) is repressed as compared with transcription on histone-free DNA. In this study, we show that human topoisomerase I (topo I) and yeast topoisomerase II (topo II), each of which relax both positive and negative superhelical tension, reverse the transcriptional repression by chromatin. In the presence of bacterial topo I, which can relax only negative superhelical tension, the transcription is repressed on chromatin templates. The data together show that the relaxation of positive superhelical tension by these enzymes was the key property required for RNA synthesis from chromatin templates. In the absence of topoisomerase, transcriptional repression on chromatin depended on RNA length. The synthesis of transcripts of 100 nt or shorter was unaffected by chromatin, but repression was apparent when the RNA transcript was 200 nt or longer. These findings suggest that transcription on chromatin templates results in the accumulation of positive superhelical tension by the elongating polymerase, which in turn inhibits further elongation in the absence of topoisomerase activity.

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Section: Discussionmentioning

confidence: 99%

Elongation by RNA polymerase II on chromatin templates requires topoisomerase activity

Mondal

2003

Nucleic Acids Research

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The interaction between p53 and DNA topoisomerase I is regulated differently in cells with wild-type and mutant p53

Gobert

Składanowski

Larsen

1999

Proc. Natl. Acad. Sci. U.S.A.

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DNA topoisomerase I is a nuclear enzyme involved in transcription, recombination, and DNA damage recognition. Previous studies have shown that topoisomerase I interacts directly with the tumor-suppressor protein p53. p53 is a transcription factor that activates certain genes through binding to specific DNA sequences. We now report that topoisomerase I can be stimulated by both latent and activated wild-type p53 as well as by several mutant and truncated p53 proteins in vitro, indicating that sequence-specific DNAbinding and stimulation of topoisomerase I are distinct properties of p53. These assays also suggest that the binding site for topoisomerase I on p53 is between amino acids 302 and 321. In living cells, the interaction between p53 and topoisomerase I is strongly dependent on p53 status. In MCF-7 cells, which have wild-type p53, the association between the two proteins is tightly regulated in a spatial and temporal manner and takes place only during brief periods of genotoxic stress. In marked contrast, the two proteins are constitutively associated in HT-29 cells, which have mutant p53. These findings have important implications for both cellular stress response and genomic stability, given the ability of topoisomerase I to recognize DNA lesions as well as to cause illegitimate recombination.DNA topoisomerase I is a nuclear enzyme essential for most aspects of nucleic acid metabolism (1). The ability of topoisomerase I to relax supercoiled DNA through transient single-stranded DNA cleavage, strand passage, and religation is needed during transcription to relieve superhelical stress (2, 3). In addition, topoisomerase I serves as a modulator of transcriptional initiation through physical interaction with transcription factors such as the TATA box-binding protein, which is a constituent of the general transcription factor IID (TFIID) complex (4, 5). This property does not require DNA cleavage but is based on protein-protein interactions. Recent results show that topoisomerase I also possesses a proteinkinase activity, which is specific for serine residues of splicing factors containing an Arg-Ser motif. Phosphorylation of these splicing factors is believed to influence gene expression by altering the splice pattern (6, 7).Eukaryotic topoisomerase I is structurally, functionally, and evolutionarily related to site-specific recombinases (8). During catalysis, topoisomerase I forms a covalent DNA-protein complex with the 3Ј end of one DNA strand. This reaction intermediate can religate with either the 5Ј hydroxyl end of the cleaved strand or with a 5Ј hydroxyl end of a heterologous DNA molecule, resulting in recombinant DNA (9, 10). In yeast, increased topoisomerase I activity is accompanied by increased levels of illegitimate recombination, whereas treatment of mammalian cells with camptothecin and other topoisomerase I-directed antitumor drugs leads to sister chromatid exchange and chromosomal aberrations (11,12). This is most likely because camptothecin treatment results in accumulation of covalent ...

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Microinjection of Anti-Topoisomerase I Immunoglobulin G Into Nuclei of Chironomus Tentans Salivary Gland Cells Leads tO Blockage of Transcription Elongation

Cited by 2 publications

References 27 publications

Elongation by RNA polymerase II on chromatin templates requires topoisomerase activity

Elongation by RNA polymerase II on chromatin templates requires topoisomerase activity

The interaction between p53 and DNA topoisomerase I is regulated differently in cells with wild-type and mutant p53

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