scholarly journals Topoisomerase 3B (TOP3B) DNA and RNA Cleavage Complexes and Pathway to Repair TOP3B-Linked RNA and DNA Breaks

2020 ◽  
Author(s):  
Sourav Saha ◽  
Yilun Sun ◽  
Shar-Yin Huang ◽  
Ukhyun Jo ◽  
Hongliang Zhang ◽  
...  
Keyword(s):  
Rna Cleavage ◽  
Dna Breaks ◽  
Dna And Rna ◽  
Rna And Dna

scholarly journals DNA and RNA Cleavage Complexes and Repair Pathway for TOP3B RNA- and DNA-Protein Crosslinks

Cell Reports ◽  
2020 ◽  
Vol 33 (13) ◽  
pp. 108569
Author(s):  
Sourav Saha ◽  
Yilun Sun ◽  
Shar-yin Naomi Huang ◽  
Simone Andrea Baechler ◽  
Lorinc Sandor Pongor ◽  
...  
Keyword(s):  
Rna Cleavage ◽  
Repair Pathway ◽  
Dna And Rna ◽  
Protein Crosslinks ◽  
Rna And Dna

scholarly journals Topoisomerase 3B (TOP3B) DNA and RNA Cleavage Complexes and Pathway to Repair TOP3B-linked RNA and DNA Breaks

2020 ◽  
Author(s):  
Sourav Saha ◽  
Yilun Sun ◽  
Shar-Yin Huang ◽  
Ukhyun Jo ◽  
Hongliang Zhang ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Dna Cleavage ◽  
E3 Ubiquitin Ligase ◽  
Proteasomal Degradation ◽  
List Type ◽  
Dna Breaks ◽  
Dna And Rna ◽  
Self Trapping ◽  
Rna And Dna

SUMMARYGenetic inactivation of TOP3B is linked with schizophrenia, autism, intellectual disability and cancer. The present study demonstrates that in vivo TOP3B forms both RNA and DNA cleavage complexes (TOP3Bccs) and reveals a pathway for repairing TOP3Bccs. For detecting cellular TOP3Bccs, we engineered a “self-trapping” mutant of TOP3B (R338W TOP3B) and to determine how human cells repair TOP3Bccs, we depleted tyrosyl-DNA phosphodiesterases (TDP1 and TDP2). TDP2-deficient cells produced elevated TOP3Bccs both in DNA and RNA. Conversely, overexpression of TDP2 lowered cellular TOP3Bccs. Using recombinant human TDP2, we demonstrate that TDP2 cannot excise the native form of TOP3Bccs. Hypothesizing that TDP2 cannot access phosphotyrosyl linkage unless TOP3B is either proteolyzed or denatured, we found that cellular TOP3Bccs are ubiquitinated by the E3 Ubiquitin Ligase TRIM41 before undergoing proteasomal degradation and excision by TDP2.HIGHLIGHTSMethod for in vivo detection of TOP3B cleavage complexes (TOP3Bccs) formed both in DNA and RNA, using a religation defective “self-trapping” R338W TOP3B mutant.First evidence that TDP2 excises TOPccs produced by a type IA topoisomerase.TDP2 processes both RNA and DNA TOP3Bccs following their ubiquitylation and proteasomal degradation inside cell.TRIM41 is the first reported E3 ubiquitin ligase for TOP3Bcc ubiquitylation and proteasomal degradation.

scholarly journals Characteristic of HPV Integration in the Genome and Transcriptome of Cervical Cancer Tissues

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Weiyang Li ◽  
Yanwei Qi ◽  
Xiaofang Cui ◽  
Qing Huo ◽  
Liangxi Zhu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Adherens Junction ◽  
Cholinergic Synapse ◽  
Cervical Cancers ◽  
Dna And Rna ◽  
Chi Squared ◽  
Integration Sites ◽  
Cancer Tissues ◽  
High Risk Hpv ◽  
Rna And Dna

High-risk HPV is clearly associated with cervical cancer. HPV integration has been confirmed to promote carcinogenesis in the previous studies. In our study, a total of 285 DNA breakpoints and 287 RNA breakpoints were collected. We analyzed the characteristic of HPV integration in the DNA and RNA samples. The results revealed that the patterns of HPV integration in RNA and DNA samples differ significantly. FHIT, KLF5, and LINC00392 were the hotspot genes integrated by HPV in the DNA samples. RAD51B, CASC8, CASC21, ERBB2, TP63, TEX41, RAP2B, and MYC were the hotspot genes integrated by HPV in RNA samples. Breakpoints of DNA samples were significantly prone to the region of INTRON (P < 0.01, Chi-squared test), whereas in the RNA samples, the breakpoints were prone to EXON. Pathway analysis had revealed that the breakpoints of RNA samples were enriched in the pathways of transcriptional misregulation in cancer, cancer pathway, and pathway of adherens junction. Breakpoints of DNA samples were enriched in the pathway of cholinergic synapse. In summary, our data helped to gain insights into the HPV integration sites in DNA and RNA samples of cervical cancer. It had provided theoretical basis for understanding the mechanism of tumorigenesis from the perspective of HPV integration in the HPV-associated cervical cancers.

scholarly journals Characterization of Microbial Community Structure in Gulf of Mexico Gas Hydrates: Comparative Analysis of DNA- and RNA-Derived Clone Libraries

2005 ◽  
Vol 71 (6) ◽  
pp. 3235-3247 ◽  
Author(s):  
Heath J. Mills ◽  
Robert J. Martinez ◽  
Sandra Story ◽  
Patricia A. Sobecky
Keyword(s):  
Phylogenetic Analysis ◽  
Microbial Community ◽  
Gulf Of Mexico ◽  
Gas Hydrate ◽  
Phylogenetic Analyses ◽  
Active Fraction ◽  
Clone Libraries ◽  
Dna And Rna ◽  
Rna And Dna

ABSTRACT The characterization of microbial assemblages within solid gas hydrate, especially those that may be physiologically active under in situ hydrate conditions, is essential to gain a better understanding of the effects and contributions of microbial activities in Gulf of Mexico (GoM) hydrate ecosystems. In this study, the composition of the Bacteria and Archaea communities was determined by 16S rRNA phylogenetic analyses of clone libraries derived from RNA and DNA extracted from sediment-entrained hydrate (SEH) and interior hydrate (IH). The hydrate was recovered from an exposed mound located in the northern GoM continental slope with a hydrate chipper designed for use on the manned-submersible Johnson Sea Link (water depth, 550 m). Previous geochemical analyses indicated that there was increased metabolic activity in the SEH compared to the IH layer (B. N. Orcutt, A. Boetius, S. K. Lugo, I. R. Macdonald, V. A. Samarkin, and S. Joye, Chem. Geol. 205:239-251). Phylogenetic analysis of RNA- and DNA-derived clones indicated that there was greater diversity in the SEH libraries than in the IH libraries. A majority of the clones obtained from the metabolically active fraction of the microbial community were most closely related to putative sulfate-reducing bacteria and anaerobic methane-oxidizing archaea. Several novel bacterial and archaeal phylotypes for which there were no previously identified closely related cultured isolates were detected in the RNA- and DNA-derived clone libraries. This study was the first phylogenetic analysis of the metabolically active fraction of the microbial community extant in the distinct SEH and IH layers of GoM gas hydrate.

scholarly journals TDP-43 mutations link Amyotrophic Lateral Sclerosis with R-loop homeostasis and R loop-mediated DNA damage

PLoS Genetics ◽  
2020 ◽  
Vol 16 (12) ◽  
pp. e1009260
Author(s):  
Marta Giannini ◽  
Aleix Bayona-Feliu ◽  
Daisy Sproviero ◽  
Sonia I. Barroso ◽  
Cristina Cereda ◽  
...  
Keyword(s):  
Dna Damage ◽  
Amyotrophic Lateral Sclerosis ◽  
Rna Binding ◽  
Neurodegenerative Disorder ◽  
Genome Instability ◽  
Neuronal Model ◽  
Dna Breaks ◽  
Dna And Rna ◽  
Double Strand Dna Breaks ◽  
Lateral Sclerosis

TDP-43 is a DNA and RNA binding protein involved in RNA processing and with structural resemblance to heterogeneous ribonucleoproteins (hnRNPs), whose depletion sensitizes neurons to double strand DNA breaks (DSBs). Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder, in which 97% of patients are familial and sporadic cases associated with TDP-43 proteinopathies and conditions clearing TDP-43 from the nucleus, but we know little about the molecular basis of the disease. After showing with the non-neuronal model of HeLa cells that TDP-43 depletion increases R loops and associated genome instability, we prove that mislocalization of mutated TDP-43 (A382T) in transfected neuronal SH-SY5Y and lymphoblastoid cell lines (LCLs) from an ALS patient cause R-loop accumulation, R loop-dependent increased DSBs and Fanconi Anemia repair centers. These results uncover a new role of TDP-43 in the control of co-transcriptional R loops and the maintenance of genome integrity by preventing harmful R-loop accumulation. Our findings thus link TDP-43 pathology to increased R loops and R loop-mediated DNA damage opening the possibility that R-loop modulation in TDP-43-defective cells might help develop ALS therapies.

scholarly journals Cleavage of DNA and RNA by PLD3 and PLD4 limits autoinflammatory triggering by multiple sensors

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Amanda L. Gavin ◽  
Deli Huang ◽  
Tanya R. Blane ◽  
Therese C. Thinnes ◽  
Yusuke Murakami ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Inflammatory Diseases ◽  
Type I ◽  
Multiple Sensors ◽  
Dna And Rna ◽  
Elevated Type ◽  
Minor Contribution ◽  
Ifn Γ ◽  
A Minor ◽  
Rna And Dna

AbstractPhospholipase D3 (PLD3) and PLD4 polymorphisms have been associated with several important inflammatory diseases. Here, we show that PLD3 and PLD4 digest ssRNA in addition to ssDNA as reported previously. Moreover, Pld3−/−Pld4−/− mice accumulate small ssRNAs and develop spontaneous fatal hemophagocytic lymphohistiocytosis (HLH) characterized by inflammatory liver damage and overproduction of Interferon (IFN)-γ. Pathology is rescued in Unc93b13d/3dPld3−/−Pld4−/− mice, which lack all endosomal TLR signaling; genetic codeficiency or antibody blockade of TLR9 or TLR7 ameliorates disease less effectively, suggesting that both RNA and DNA sensing by TLRs contributes to inflammation. IFN-γ made a minor contribution to pathology. Elevated type I IFN and some other remaining perturbations in Unc93b13d/3dPld3−/−Pld4−/− mice requires STING (Tmem173). Our results show that PLD3 and PLD4 regulate both endosomal TLR and cytoplasmic/STING nucleic acid sensing pathways and have implications for the treatment of nucleic acid-driven inflammatory disease.

scholarly journals GeTallele: a method for integrative analysis and visualization of DNA and RNA allele frequencies

2018 ◽  
Author(s):  
Piotr Słowiński ◽  
Muzi Li ◽  
Paula Restrepo ◽  
Nawaf Alomran ◽  
Liam F. Spurr ◽  
...  
Keyword(s):  
Gene Dosage ◽  
Transcriptional Response ◽  
Structural Features ◽  
Integrative Analysis ◽  
Allele Frequencies ◽  
Biological Traits ◽  
Specific Expression ◽  
Dna And Rna ◽  
Wide Range ◽  
Rna And Dna

AbstractBackgroundAsymmetric allele expression typically indicates functional and/or structural features associated with the underlying genetic variants. When integrated, RNA and DNA allele frequencies can reveal patterns characteristic of a wide-range of biological traits, including ploidy changes, genome admixture, allele-specific expression and gene-dosage transcriptional response.ResultsTo assess RNA and DNA allele frequencies from matched sequencing datasets, we introduce a method for generating model distributions of variant allele frequencies (VAF) with a given variant read probability. In contrast to other methods, based on whole sequences or single SNV, proposed methodology uses continuous multi-SNV genomic regions. The methodology is implemented in a GeTallele toolbox that provides a suite of functions for integrative analysis, statistical assessment and visualization of Genome and Transcriptome allele frequencies. Using model VAF probabilities, GeTallele allows estimation and comparison of variant read probabilities (VAF distributions) in a sequencing dataset. We demonstrate this functionality across cancer DNA and RNA sequencing datasets.ConclusionBased on our evaluation, variant read probabilities can serve as a dependable indicator to assess gene and chromosomal allele asymmetries and to aid calls of genomic events in matched sequencing RNA and DNA [email protected]

Concurrent targeted resequencing for translocations and mutations in tumor samples.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14597-e14597
Author(s):  
Li Chen
Keyword(s):  
Lung Tumor ◽  
Variant Calling ◽  
Limited Information ◽  
Tissue Samples ◽  
Single Tube ◽  
Targeted Resequencing ◽  
Pik3ca Mutations ◽  
Dna And Rna ◽  
Exon 19 Deletion ◽  
Rna And Dna

e14597 Background: Genetic variations are diverse, and proper nucleic acid templates should be analyzed for optimal outcomes. Previous NGS assays separately treat DNA and/or RNA, and are costly and produce limited information. Here we present a concurrent assay simultaneously converting both RNA and DNA templates in a single-tube format to streamline variant detection process. Methods: We developed a high-throughput targeted resequencing assay utilizing both DNA and RNA templates for mutation and fusion detection, and applied to a cohort of over 1000 lung tumor samples. Total nucleic acids from tissue samples were processed in a single-tube format throughout, and post-assay data analysis split RNA and DNA signals for corresponding variant calling. Sensitivity and specificity were sufficient for tissue samples. Results: In addition to common EGFR, KRAS, BRAF, PIK3CA mutations and ALK, ROS1, RET fusions and MET Exon 14 skipping, we also identified rare HLA-DRB1---MET and MSN---NTRK2 fusions. We found that MET exon 14 skipping was abundant, and that EGFR T790M is more associated with Exon 19 deletion than with L858R. We also found baseline mutation frequency for FFPE samples at 4-5%. Conclusions: Overall, this method is robust and convenient for clinical molecular diagnosis for tissue samples where variant types are diverse and time and budgets are constrained. Extreme caution is suggested for making positive calls below 5% MAF.

Comparing Ion Distributions around RNA and DNA Helical and Loop-loop Motifs

2008 ◽  
Vol 1130 ◽  
Author(s):  
Andrey V Semichaevsky ◽  
Ashley E Marlowe ◽  
Yaroslava G Yingling
Keyword(s):  
Self Assembly ◽  
The Self ◽  
Assembly Process ◽  
Dna Motifs ◽  
Dna And Rna ◽  
Ion Distributions ◽  
Concentration Of Ions ◽  
The Stability ◽  
Dynamics Simulations ◽  
Rna And Dna

AbstractNucleic acid nanoparticles can self-assembly through the formation of complementary loop-loop interactions or stem-stem interactions. Presence and concentration of ions can significantly affect the self-assembly process and the stability of the nanostructure. In this paper we use explicit molecular dynamics simulations to examine the variations in cationic distributions around DNA and RNA helices and loop-loop interactions with identical sequence except for Thymine to Uracil substitution. Our simulations show that the ionic distributions are different around RNA and DNA motifs which could be related to the discrepancy in stability of loop-loop complexes.

Sign in / Sign up

Export Citation Format

Share Document