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. We show that E2-dependent R-loop formation and breast cancer rearrangements are highly enriched at E2-responsive genomic loci and that E2 induces DNA replication-dependent double-strand breaks (DSBs). Strikingly, many DSBs that accumulate in response to E2 are R-loop dependent. Thus, R-loops resulting from the E2 transcriptional response are a significant source of DNA damage. This work reveals a novel mechanism by which E2 stimulation leads to genomic instability and highlights how transcriptional programs play an important role in shaping the genomic landscape of DNA damage susceptibility

A cloud storage overlay to aggregate heterogeneous cloud services

Many Cloud services provide generic (e.g., Amazon S3 or Dropbox) or data-specific Cloud storage (e.g., Google Picasa or SoundCloud). Although both Cloud storage service types have the data storage in common, they present heterogeneous characteristics: different interfaces, accounting and charging schemes, privacy and security levels, functionality and, among the data-specific Cloud storage services, different data type restrictions. This paper proposes PiCsMu (Platform-independent Cloud Storage System for Multiple Usage), a novel approach exploiting heterogeneous data storage of different Cloud services by building a Cloud storage overlay, which aggregates multiple Cloud storage services, provides enhanced privacy, and offers a distributed file sharing system. As opposed to P2P file sharing, where data and indices are stored on peers, PiCsMu uses Cloud storage systems for data storage, while maintaining a distributed index. The main contribution of this work is to show the feasibility to store arbitrary data in different Cloud services for private use and/or for file sharing. Furthermore, the evaluation of the prototype confirms the scalability with respect to different file sizes and also shows that a moderate overhead in terms of storage and processing time is required

A survey of cloud services and potential applications of social awareness

The variety of emerging cloud services and applications manifests in a multitude of network and hardware requirements, but also in different service and traffic characteristics. Due to the popularity of clouds, a set of issues emerges for the different stakeholders involved in providing and delivering cloud services to the end user. Not only pure network layer optimization, but especially the new field of socially-aware traffic management seems promising to overcome these issues. In this paper, the applicability of social awareness to different types of cloud services is discussed. For that purpose, cloud applications are classified according to relevant technical and non-technical characteristics. Based on this novel classification scheme, the benefits and challenges of social awareness are discussed and examples for the optimization of cloud services are given

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

International audienceRNA 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. The 719-member-strong Yangshan virus assemblage is the sister clade to the expansive class Alsuviricetes and consists of viruses with simple genomes that typically encode only RNA-dependent RNA polymerase (RdRP), capping enzyme and capsid protein. Several clades within the Yangshan assemblage independently evolved domain permutation in the RdRP. Another previously unknown clade shares ancestry with Potyviridae, the largest known plant virus family. The 'Aquatic picorna-like viruses/Marnaviridae' clade was greatly expanded, with more than 800 added viruses. Several RdRP-linked protein domains not previously detected in any RNA viruses were identified, such as the small ubiquitin-like modifier (SUMO) domain, phospholipase A2 and PrsW-family protease domain. Multiple viruses utilize alternative genetic codes implying protist (especially ciliate) hosts. The results reveal a vast RNA virome that includes many previously unknown groups. However, phylogenetic analysis of the RdRPs supports the previously established five-branch structure of the RNA virus evolutionary tree, with no additional phyla

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 instability1, which has been linked to the action of endonucleases such as XPG2–4. However, the mechanisms and cellular consequences of such processing have remained unclear. Here we identify a new population of RNA–DNA hybrids in the cytoplasm that are R-loop-processing products. When nuclear R-loops were perturbed by depleting the RNA–DNA helicase senataxin (SETX) or the breast cancer gene BRCA1 (refs. 5–7), we observed XPG- and XPF-dependent cytoplasmic hybrid formation. We identify their source as a subset of stable, overlapping nuclear hybrids with a specific nucleotide signature. Cytoplasmic hybrids bind to the pattern recognition receptors cGAS and TLR3 (ref. 8), activating IRF3 and inducing apoptosis. Excised hybrids and an R-loop-induced innate immune response were also observed in SETX-mutated cells from patients with ataxia oculomotor apraxia type 2 (ref. 9) and in BRCA1-mutated cancer cells10. These findings establish RNA–DNA hybrids as immunogenic species that aberrantly accumulate in the cytoplasm after R-loop processing, linking R-loop accumulation to cell death through the innate immune response. Aberrant R-loop processing and subsequent innate immune activation may contribute to many diseases, such as neurodegeneration and cancer