R-loop-derived cytoplasmic RNA-DNA hybrids activate an immune response.

R-loops are RNA-DNA-hybrid-containing nucleic acids with important cellular roles. Deregulation of R-loop dynamics can lead to DNA damage and genome instability, which has been linked to the action of endonucleases such as XPG. However, the mechanisms and cellular consequences of such processing have remained unclear.

Doubling of the known set of RNA viruses by metagenomic analysis of an aquatic virome.

RNA viruses in aquatic environments remain poorly studied. Here, we analysed the RNA virome from approximately 10 l water from Yangshan Deep-Water Harbour near the Yangtze River estuary in China and identified more than 4,500 distinct RNA viruses, doubling the previously known set of viruses. Phylogenomic analysis identified several major lineages, roughly, at the taxonomic ranks of class, order and family.

qDRIP: a method to quantitatively assess RNA-DNA hybrid formation genome-wide.

R-loops are dynamic, co-transcriptional nucleic acid structures that facilitate physiological processes but can also cause DNA damage in certain contexts. Perturbations of transcription or R-loop resolution are expected to change their genomic distribution. Next-generation sequencing approaches to map RNA-DNA hybrids, a component of R-loops, have so far not allowed quantitative comparisons between such conditions.

R-Loops as Cellular Regulators and Genomic Threats.

During transcription, the nascent RNA strand can base pair with its template DNA, displacing the non-template strand as ssDNA and forming a structure called an R-loop. R-loops are common across many domains of life and cause DNA damage in certain contexts. In this review, we summarize recent results implicating R-loops as important regulators of cellular processes such as transcription termination, gene regulation, and DNA repair.

An intrinsic S/G checkpoint enforced by ATR.

The cell cycle is strictly ordered to ensure faithful genome duplication and chromosome segregation. Control mechanisms establish this order by dictating when a cell transitions from one phase to the next. Much is known about the control of the G/S, G/M, and metaphase/anaphase transitions, but thus far, no control mechanism has been identified for the S/G transition.

Transcription-Replication Conflict Orientation Modulates R-Loop Levels and Activates Distinct DNA Damage Responses.

Conflicts between transcription and replication are a potent source of DNA damage. Co-transcriptional R-loops could aggravate such conflicts by creating an additional barrier to replication fork progression. Here, we use a defined episomal system to investigate how conflict orientation and R-loop formation influence genome stability in human cells.

Co-transcriptional R-loops are the main cause of estrogen-induced DNA damage.

The hormone estrogen (E2) binds the estrogen receptor to promote transcription of E2-responsive genes in the breast and other tissues. E2 also has links to genomic instability, and elevated E2 levels are tied to breast cancer. Here, we show that E2 stimulation causes a rapid, global increase in the formation of R-loops, co-transcriptional RNA-DNA products, which in some instances have been linked to DNA damage.

Multivalent display of pendant pro-apoptotic peptides increases cytotoxic activity.

Several cationic antimicrobial peptides have been investigated as potential anti-cancer drugs due to their demonstrated selective toxicity towards cancer cells relative to normal cells. For example, intracellular delivery of KLA, a pro-apoptotic peptide, results in toxicity against a variety of cancer cell lines; however, the relatively low activity and small size lead to rapid renal excretion when applied in vivo, limiting its therapeutic potential. In this work, apoptotic peptide-polymer hybrid materials were developed to increase apoptotic peptide activity via multivalent display.

Memantine for the prevention of primary headache disorders.

Objective: To describe the current data evaluating the efficacy and safety of memantine for the prevention of primary headache disorders.

Data Sources: A literature search using MEDLINE (1966-July 2014) and EMBASE (1973-July 2014) was conducted using the search terms memantine, headache, migraine, glutamate, and NMDA. References of identified articles were reviewed for additional, relevant citations.

Optimization of Tet1 ligand density in HPMA-co-oligolysine copolymers for targeted neuronal gene delivery.

Targeted gene delivery vectors can enhance cellular specificity and transfection efficiency. We demonstrated previously that conjugation of Tet1, a peptide that binds to the GT1b ganglioside, to polyethylenimine results in preferential transfection of neural progenitor cells in vivo. In this work, we investigate the effect of Tet1 ligand density on gene delivery to neuron-like, differentiated PC-12 cells.