keyword
MENU ▼
Read by QxMD icon Read
search

"R-loops"

keyword
https://www.readbyqxmd.com/read/29674319/long-repeating-ttaggg-n-single-stranded-dna-self-condenses-into-compact-beaded-filaments-stabilized-by-g-quadruplex-formation
#1
Anirban Kar, Nathan Jones, N Özlem Arat, Richard Fishel, Jack Griffith
Conformations adopted by long stretches of single stranded DNA (ssDNA) are of central interest in understanding the architecture of replication forks, R loops, and other structures generated during DNA metabolism in vivo. This is particularly so if the ssDNA consists of short nucleotide repeats. Such studies have been hampered by the lack of defined substrates greater than ~150 nt, and the absence of high-resolution biophysical approaches. Here we describe the generation of very long ssDNA consisting of the mammalian telomeric repeat (5'-TTAGGG-3')n as well as the interrogation of its structure by electron microscopy (EM) and single molecule magnetic tweezers (smMT)...
April 19, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29658469/-r-loop-associated-genetic-instability-why-introns-matter
#2
Benoit Palancade
No abstract text is available yet for this article.
April 2018: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/29657305/strengths-and-weaknesses-of-the-current-strategies-to-map-and-characterize-r-loops
#3
REVIEW
Vincent Vanoosthuyse
R-loops are evolutionarily conserved three-stranded structures that result from the formation of stable DNA:RNA hybrids in the genome. R-loops have attracted increasing interest in recent years as potent regulators of gene expression and genome stability. In particular, their strong association with severe replication stress makes them potential oncogenic structures. Despite their importance, the rules that govern their formation and their dynamics are still controversial and an in-depth description of their direct impact on chromatin organization and DNA transactions is still lacking...
March 27, 2018: Non-Coding RNA
https://www.readbyqxmd.com/read/29629374/rna-surveillance-by-the-nuclear-rna-exosome-mechanisms-and-significance
#4
Koichi Ogami, Yaqiong Chen, James L Manley
The nuclear RNA exosome is an essential and versatile machinery that regulates maturation and degradation of a huge plethora of RNA species. The past two decades have witnessed remarkable progress in understanding the whole picture of its RNA substrates and the structural basis of its functions. In addition to the exosome itself, recent studies focusing on associated co-factors have been elucidating how the exosome is directed towards specific substrates. Moreover, it has been gradually realized that loss-of-function of exosome subunits affect multiple biological processes such as the DNA damage response, R-loop resolution, maintenance of genome integrity, RNA export, translation and cell differentiation...
2018: Non-Coding RNA
https://www.readbyqxmd.com/read/29622660/rnase-h-eliminates-r-loops-that-disrupt-dna-replication-but-is-nonessential-for-efficient-dsb-repair
#5
Hongchang Zhao, Min Zhu, Oliver Limbo, Paul Russell
In Saccharomyces cerevisiae , genome stability depends on RNases H1 and H2, which remove ribonucleotides from DNA and eliminate RNA-DNA hybrids (R-loops). In Schizosaccharomyces pombe , RNase H enzymes were reported to process RNA-DNA hybrids produced at a double-strand break (DSB) generated by I-PpoI meganuclease. However, it is unclear if RNase H is generally required for efficient DSB repair in fission yeast, or whether it has other genome protection roles. Here, we show that S. pombe rnh1∆ rnh201∆ cells, which lack the RNase H enzymes, accumulate R-loops and activate DNA damage checkpoints...
April 5, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29617652/multifaceted-impact-of-microrna-493-5p-on-genome-stabilizing-pathways-induces-platinum-and-parp-inhibitor-resistance-in-brca2-mutated-carcinomas
#6
Khyati Meghani, Walker Fuchs, Alexandre Detappe, Pascal Drané, Ewa Gogola, Sven Rottenberg, Jos Jonkers, Ursula Matulonis, Elizabeth M Swisher, Panagiotis A Konstantinopoulos, Dipanjan Chowdhury
BRCA1/2-mutated ovarian cancers (OCs) are defective in homologous recombination repair (HRR) of double-strand breaks (DSBs) and thereby sensitive to platinum and PARP inhibitors (PARPis). Multiple PARPis have recently received US Food and Drug Administration (FDA) approval for treatment of OCs, and resistance to PARPis is a major clinical problem. Utilizing primary and recurrent BRCA1/2-mutated carcinomas from OC patients, patient-derived lines, and an in vivo BRCA2-mutated mouse model, we identified a microRNA, miR-493-5p, that induced platinum/PARPi resistance exclusively in BRCA2-mutated carcinomas...
April 3, 2018: Cell Reports
https://www.readbyqxmd.com/read/29600804/author-correction-attenuation-of-rna-polymerase-ii-pausing-mitigates-brca1-associated-r-loop-accumulation-and-tumorigenesis
#7
Xiaowen Zhang, Huai-Chin Chiang, Yao Wang, Chi Zhang, Sabrina Smith, Xiayan Zhao, Sreejith J Nair, Joel Michalek, Ismail Jatoi, Meeghan Lautner, Boyce Oliver, Howard Wang, Anna Petit, Teresa Soler, Joan Brunet, Francesca Mateo, Miguel Angel Pujana, Elizabeth Poggi, Krysta Chaldekas, Claudine Isaacs, Beth N Peshkin, Oscar Ochoa, Frederic Chedin, Constantine Theoharis, Lu-Zhe Sun, Tyler J Curiel, Richard Elledge, Victor X Jin, Yanfen Hu, Rong Li
This corrects the article DOI: 10.1038/ncomms15908.
March 30, 2018: Nature Communications
https://www.readbyqxmd.com/read/29584802/perturbed-autophagy-and-dna-repair-converge-to-promote-neurodegeneration-in-amyotrophic-lateral-sclerosis-and-dementia
#8
Callum Walker, Sherif F El-Khamisy
Maintaining genomic stability constitutes a major challenge facing cells. DNA breaks can arise from direct oxidative damage to the DNA backbone, the inappropriate activities of endogenous enzymes such as DNA topoisomerases, or due to transcriptionally-derived RNA/DNA hybrids (R-loops). The progressive accumulation of DNA breaks has been linked to several neurological disorders. Recently, however, several independent studies have implicated nuclear and mitochondrial genomic instability, perturbed co-transcriptional processing, and impaired cellular clearance pathways as causal and intertwined mechanisms underpinning neurodegeneration...
March 23, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29549141/ewing-sarcomas-phenocopy-brca1-deficient-tumors
#9
(no author information available yet)
Transcriptional dysregulation promotes R-loops and impairs homologous recombination in Ewing sarcoma.
March 16, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29513652/ews-fli1-increases-transcription-to-cause-r-loops-and-block-brca1-repair-in-ewing-sarcoma
#10
Aparna Gorthi, July Carolina Romero, Eva Loranc, Lin Cao, Liesl A Lawrence, Elicia Goodale, Amanda Balboni Iniguez, Xavier Bernard, V Pragathi Masamsetti, Sydney Roston, Elizabeth R Lawlor, Jeffrey A Toretsky, Kimberly Stegmaier, Stephen L Lessnick, Yidong Chen, Alexander J R Bishop
Ewing sarcoma is an aggressive paediatric cancer of the bone and soft tissue. It results from a chromosomal translocation, predominantly t(11;22)(q24:q12), that fuses the N-terminal transactivation domain of the constitutively expressed EWSR1 protein with the C-terminal DNA binding domain of the rarely expressed FLI1 protein. Ewing sarcoma is highly sensitive to genotoxic agents such as etoposide, but the underlying molecular basis of this sensitivity is unclear. Here we show that Ewing sarcoma cells display alterations in regulation of damage-induced transcription, accumulation of R-loops and increased replication stress...
March 15, 2018: Nature
https://www.readbyqxmd.com/read/29474582/genome-wide-relationship-between-r-loop-formation-and-antisense-transcription-in-escherichia-coli
#11
Nalini Raghunathan, Rajvardhan M Kapshikar, Jakku K Leela, Jillella Mallikarjun, Philippe Bouloc, Jayaraman Gowrishankar
Transcription termination by Rho is essential for viability in various bacteria, including some major pathogens. Since Rho acts by targeting nascent RNAs that are not simultaneously translated, it also regulates antisense transcription. Here we show that RNase H-deficient mutants of Escherichia coli exhibit heightened sensitivity to the Rho inhibitor bicyclomycin, and that Rho deficiency provokes increased formation of RNA-DNA hybrids (R-loops) which is ameliorated by expression of the phage T4-derived R-loop helicase UvsW...
February 21, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29471495/arginine-methylation-of-the-c-terminus-rgg-motif-promotes-top3b-topoisomerase-activity-and-stress-granule-localization
#12
Lifeng Huang, Zhihao Wang, Nithya Narayanan, Yanzhong Yang
DNA topoisomerase 3B (TOP3B) is unique among all mammalian topoisomerases for its dual activities that resolve both DNA and RNA topological entanglements to facilitate transcription and translation. However, the mechanism by which TOP3B activity is regulated is still elusive. Here, we have identified arginine methylation as an important post-translational modification (PTM) for TOP3B activity. Protein arginine methyltransferase (PRMT) 1, PRMT3 and PRMT6 all methylate TOP3B in vitro at its C-terminal arginine (R) and glycine (G)-rich motif...
February 19, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29447396/rna-dna-hybrids-promote-the-expansion-of-friedreich-s-ataxia-gaa-n-repeats-via-break-induced-replication
#13
Alexander J Neil, Miranda U Liang, Alexandra N Khristich, Kartik A Shah, Sergei M Mirkin
Expansion of simple DNA repeats is responsible for numerous hereditary diseases in humans. The role of DNA replication, repair and transcription in the expansion process has been well documented. Here we analyzed, in a yeast experimental system, the role of RNA-DNA hybrids in genetic instability of long (GAA)n repeats, which cause Friedreich's ataxia. Knocking out both yeast RNase H enzymes, which counteract the formation of RNA-DNA hybrids, increased (GAA)n repeat expansion and contraction rates when the repetitive sequence was transcribed...
February 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29439150/myelodysplastic-syndrome-splicing-factor-mutations-induce-r-loops
#14
(no author information available yet)
Mutations in SRSF2 and U2AF35 trigger replication stress and ATR activation via R-loop formation.
February 9, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29419415/spliceosomal-components-protect-embryonic-neurons-from-r-loop-mediated-dna-damage-and-apoptosis
#15
Shelly Sorrells, Sara Nik, Mattie Casey, Rosannah C Cameron, Harold Truong, Cristhian Toruno, Michelle Gulfo, Albert Lowe, Cicely Jette, Rodney A Stewart, Teresa V Bowman
RNA splicing factors are essential for the viability of all eukaryotic cells; however, in metazoans some cell types are exquisitely sensitive to disruption of splicing factors, such as neuronal cells which can lead to neurodegenerative diseases. The basis for this tissue selectivity is not well understood due to difficulties in analyzing the consequences of splicing factor defects in whole animal systems. Here, we use zebrafish mutants to show that loss of spliceosomal components, including splicing factor 3b, subunit 1 (sf3b1), caused increased DNA double-strand breaks and apoptosis in embryonic neurons with a concomitant accumulation of R-loops, which are non-canonical nucleic acid structures that promote genomic instability...
January 29, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29404398/gene-gating-at-nuclear-pores-prevents-the-formation-of-r-loops
#16
Hélène Gaillard, Francisco García-Benítez, Andrés Aguilera
Transcription is an important source of genetic variability. A large amount of transcription-associated genome variation arises from the unscheduled formation of R loops. We have recently found that physical proximity of chromatin to nuclear pores prevents the formation of pathological R loops during transcription. Our study opens new perspectives to understand genome stability as a function of nuclear location.
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/29395064/senataxin-mutation-reveals-how-r-loops-promote-transcription-by-blocking-dna-methylation-at-gene-promoters
#17
Christopher Grunseich, Isabel X Wang, Jason A Watts, Joshua T Burdick, Robert D Guber, Zhengwei Zhu, Alan Bruzel, Tyler Lanman, Kelian Chen, Alice B Schindler, Nancy Edwards, Abhik Ray-Chaudhury, Jianhua Yao, Tanya Lehky, Grzegorz Piszczek, Barbara Crain, Kenneth H Fischbeck, Vivian G Cheung
R-loops are three-stranded nucleic acid structures found abundantly and yet often viewed as by-products of transcription. Studying cells from patients with a motor neuron disease (amyotrophic lateral sclerosis 4 [ALS4]) caused by a mutation in senataxin, we uncovered how R-loops promote transcription. In ALS4 patients, the senataxin mutation depletes R-loops with a consequent effect on gene expression. With fewer R-loops in ALS4 cells, the expression of BAMBI, a negative regulator of transforming growth factor β (TGF-β), is reduced; that then leads to the activation of the TGF-β pathway...
February 1, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29395063/the-augmented-r-loop-is-a-unifying-mechanism-for-myelodysplastic-syndromes-induced-by-high-risk-splicing-factor-mutations
#18
Liang Chen, Jia-Yu Chen, Yi-Jou Huang, Ying Gu, Jinsong Qiu, Hao Qian, Changwei Shao, Xuan Zhang, Jing Hu, Hairi Li, Shunmin He, Yu Zhou, Omar Abdel-Wahab, Dong-Er Zhang, Xiang-Dong Fu
Mutations in several general pre-mRNA splicing factors have been linked to myelodysplastic syndromes (MDSs) and solid tumors. These mutations have generally been assumed to cause disease by the resultant splicing defects, but different mutations appear to induce distinct splicing defects, raising the possibility that an alternative common mechanism is involved. Here we report a chain of events triggered by multiple splicing factor mutations, especially high-risk alleles in SRSF2 and U2AF1, including elevated R-loops, replication stress, and activation of the ataxia telangiectasia and Rad3-related protein (ATR)-Chk1 pathway...
February 1, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29394375/replication-stress-induces-accumulation-of-fancd2-at-central-region-of-large-fragile-genes
#19
Yusuke Okamoto, Watal M Iwasaki, Kazuto Kugou, Kazuki K Takahashi, Arisa Oda, Koichi Sato, Wataru Kobayashi, Hidehiko Kawai, Ryo Sakasai, Akifumi Takaori-Kondo, Takashi Yamamoto, Masato T Kanemaki, Masato Taoka, Toshiaki Isobe, Hitoshi Kurumizaka, Hideki Innan, Kunihiro Ohta, Masamichi Ishiai, Minoru Takata
During mild replication stress provoked by low dose aphidicolin (APH) treatment, the key Fanconi anemia protein FANCD2 accumulates on common fragile sites, observed as sister foci, and protects genome stability. To gain further insights into FANCD2 function and its regulatory mechanisms, we examined the genome-wide chromatin localization of FANCD2 in this setting by ChIP-seq analysis. We found that FANCD2 mostly accumulates in the central regions of a set of large transcribed genes that were extensively overlapped with known CFS...
January 31, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29386125/brca2-regulates-transcription-elongation-by-rna-polymerase-ii-to-prevent-r-loop-accumulation
#20
Mahmud K K Shivji, Xavier Renaudin, Çiğdem H Williams, Ashok R Venkitaraman
The controlled release of RNA polymerase II (RNAPII) from promoter-proximal pausing (PPP) sites is critical for transcription elongation in metazoans. We show that the human tumor suppressor BRCA2 interacts with RNAPII to regulate PPP release, thereby preventing unscheduled RNA-DNA hybrids (R-loops) implicated in genomic instability and carcinogenesis. BRCA2 inactivation by depletion or cancer-causing mutations instigates RNAPII accumulation and R-loop accrual at PPP sites in actively transcribed genes, accompanied by γH2AX formation marking DNA breakage, which is reduced by ERCC4 endonuclease depletion...
January 23, 2018: Cell Reports
keyword
keyword
70413
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"