Topoisomerase-mediated chromosomal break repair: an emerging player in many games

Ashour, Mohamed E.; Atteya, Reham; El‐Khamisy, Sherif F.

doi:10.1038/nrc3892

Cited by 151 publications

(143 citation statements)

References 172 publications

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“…In Arabidopsis, TOP1a affects nucleosome distribution and is required for PcG-mediated repression of gene expression . To clarify whether the TOP1a effect on FLC expression is relevant to changes in nucleosome occupancy, we examined the occupancy of the +1 nucleosome, which is located about 70 bp 39 to the transcription start site of the FLC locus, as reported previously (Ashour et al, 2015;Finnegan, 2015). There was no obvious difference in nucleosome density at FLC between wild-type and top1a-10 seedlings evaluated by histone H3 ChIP (Supplemental Fig.…”

Section: Top1a Does Not Affect Nucleosome Occupancy At Flc Maf4 Andmentioning

confidence: 80%

“…These topoisomerases are classified into types I and II, which cleave and reseal single-strand and double-strand breaks, respectively (Wang, 2002;Ashour et al, 2015). Topoisomerase I (TOP1) plays a specific role in relaxing both positive and negative supercoiling by creating a single-strand DNA break and rotating the broken strand around the TOP1-bound DNA strand.…”

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confidence: 99%

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DNA Topoisomerase Iα Affects the Floral Transition

et al. 2016

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ORCID ID: 0000-0002-9778-8855 (H.Y.).DNA topoisomerases modulate DNA topology to maintain chromosome superstructure and genome integrity, which is indispensable for DNA replication and RNA transcription. Their function in plant development still remains largely unknown. Here, we report a hitherto unidentified role of Topoisomerase Ia (TOP1a) in controlling flowering time in Arabidopsis (Arabidopsis thaliana). Loss of function of TOP1a results in early flowering under both long and short days. This is attributed mainly to a decrease in the expression of a central flowering repressor, FLOWERING LOCUS C (FLC), and its close homologs, MADS AFFECTING FLOWERING4 (MAF4) and MAF5, during the floral transition. TOP1a physically binds to the genomic regions of FLC, MAF4, and MAF5 and promotes the association of RNA polymerase II complexes to their transcriptional start sites. These correlate with the changes in histone modifications but do not directly affect nucleosome occupancy at these loci. Our results suggest that TOP1a mediates DNA topology to facilitate the recruitment of RNA polymerase II at FLC, MAF4, and MAF5 in conjunction with histone modifications, thus facilitating the expression of these key flowering repressors to prevent precocious flowering in Arabidopsis.

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Section: Top1a Does Not Affect Nucleosome Occupancy At Flc Maf4 Andmentioning

confidence: 80%

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confidence: 99%

DNA Topoisomerase Iα Affects the Floral Transition

et al. 2016

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“…cell lines). Four RNA transcripts implicated in the repair of protein-linked DNA breaks were tested using specific nanoprobes for each transcript (Ashour et al, 2015, Elsayed et al, 2016, Meisenberg et al, 2016). In agreement with HCV detection, the results of the additional four transcripts confirm the broad utility of the biosensor technology in RNA detection (Fig.…”

Section: Resultsmentioning

confidence: 99%

Gold aggregating gold: A novel nanoparticle biosensor approach for the direct quantification of hepatitis C virus RNA in clinical samples

Shawky

Awad

Allam

et al. 2017

Biosensors and Bioelectronics

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The affordable and reliable detection of Hepatitis C Virus (HCV) RNA is a cornerstone in the management and control of infection, affecting approximately 3% of the global population. However, the existing technologies are expensive, labor intensive and time consuming, posing significant limitations to their wide-scale exploitation, particularly in economically deprived populations. Here, we utilized the unique optical and physicochemical properties of gold nanoparticles (AuNPs) to develop a novel assay platform shown to be rapid and robust in sensing and quantifying unamplified HCV RNA in clinical samples. The assay is based on inducing aggregation of citrate AuNPs decorated with a specific nucleic acid probe. Two types of cationic AuNPs, cysteamine and CTAB capped, were compared to achieve maximum assay performance. The technology is simple, rapid, cost effective and quantitative with 93.3% sensitivity, high specificity and detection limit of 4.57 IU/µl. Finally, our data suggest that RNA folding impact the aggregation behavior of the functionalized AuNPs, with broader applications in other nucleic acid detection technologies.

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“…TDP2 hydrolyzes 5 ′ phosphodiester bonds specifically but requires TOP2 proteolytic degradation to expose the protein-DNA linkage (Gao et al 2014;Ashour et al 2015). The use of CIP to release the DNA is simpler because it is carried out directly on the bead-bound TOP2 without protease digestion.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide TOP2A DNA cleavage is biased toward translocated and highly transcribed loci

Davenport

Urtishak

et al. 2017

Genome Res.

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Type II topoisomerases orchestrate proper DNA topology, and they are the targets of anti-cancer drugs that cause treatment-related leukemias with balanced translocations. Here, we develop a high-throughput sequencing technology to define TOP2 cleavage sites at single-base precision, and use the technology to characterize TOP2A cleavage genome-wide in the human K562 leukemia cell line. We find that TOP2A cleavage has functionally conserved local sequence preferences, occurs in cleavage cluster regions (CCRs), and is enriched in introns and lincRNA loci. TOP2A CCRs are biased toward the distal regions of gene bodies, and TOP2 poisons cause a proximal shift in their distribution. We find high TOP2A cleavage levels in genes involved in translocations in TOP2 poison-related leukemia. In addition, we find that a large proportion of genes involved in oncogenic translocations overall contain TOP2A CCRs. The TOP2A cleavage of coding and lincRNA genes is independently associated with both length and transcript abundance. Comparisons to ENCODE data reveal distinct TOP2A CCR clusters that overlap with marks of transcription, open chromatin, and enhancers. Our findings implicate TOP2A cleavage as a broad DNA damage mechanism in oncogenic translocations as well as a functional role of TOP2A cleavage in regulating transcription elongation and gene activation.

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Topoisomerase-mediated chromosomal break repair: an emerging player in many games

Cited by 151 publications

References 172 publications

DNA Topoisomerase Iα Affects the Floral Transition

DNA Topoisomerase Iα Affects the Floral Transition

Gold aggregating gold: A novel nanoparticle biosensor approach for the direct quantification of hepatitis C virus RNA in clinical samples

Genome-wide TOP2A DNA cleavage is biased toward translocated and highly transcribed loci

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