Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication

Early tumorigenesis is associated with the engagement of the DNA-damage checkpoint response (DDR). Cell proliferation and transformation induced by oncogene activation are restrained by cellular senescence. It is unclear whether DDR activation and oncogene-induced senescence (OIS) are causally linked. Here we show that senescence, triggered by the expression of an activated oncogene (H-RasV12) in normal human cells, is a consequence of the activation of a robust DDR. Experimental inactivation of DDR abrogates OIS and promotes cell transformation. DDR and OIS are established after a hyper-replicative phase occurring immediately after oncogene expression. Senescent cells arrest with partly replicated DNA and with DNA replication origins having fired multiple times. In vivo DNA labelling and molecular DNA combing reveal that oncogene activation leads to augmented numbers of active replicons and to alterations in DNA replication fork progression. We also show that oncogene expression does not trigger a DDR in the absence of DNA replication. Last, we show that oncogene activation is associated with DDR activation in a mouse model in vivo. We propose that OIS results from the enforcement of a DDR triggered by oncogene-induced DNA hyper-replication.     

The earliest record of human activity in northern Europe

The colonization of Eurasia by early humans is a key event after their spread out of Africa, but the nature, timing and ecological context of the earliest human occupation of northwest Europe is uncertain and has been the subject of intense debate. The southern Caucasus was occupied about 1.8 million years (Myr) ago, whereas human remains from Atapuerca-TD6, Spain (more than 780 kyr ago) and Ceprano, Italy (about 800 kyr ago) show that early Homo had dispersed to the Mediterranean hinterland before the Brunhes-Matuyama magnetic polarity reversal (780 kyr ago). Until now, the earliest uncontested artefacts from northern Europe were much younger, suggesting that humans were unable to colonize northern latitudes until about 500 kyr ago. Here we report flint artefacts from the Cromer Forest-bed Formation at Pakefield (52 degrees N), Suffolk, UK, from an interglacial sequence yielding a diverse range of plant and animal fossils. Event and lithostratigraphy, palaeomagnetism, amino acid geochronology and biostratigraphy indicate that the artefacts date to the early part of the Brunhes Chron (about 700 kyr ago) and thus represent the earliest unequivocal evidence for human presence north of the Alps.     

Additional new species of Grouvellinus Champion 1923 (Insecta,Coleoptera, Elmidae) discovered by citizen scientists and DNA barcoded in the field applying a novel MinION-based workflow

ABSTRACT

Four new species, Grouvellinus nigerquadratus sp. nov., G. cruxniger sp. nov., G. luciaensis sp. nov., and G. borneensis sp. nov., are described from Borneo and illustrated in detail. Two additional species of the genus which remain undescribed are briefly diagnosed. The material was collected during Taxon Expeditions’ field course which involved citizen scientists, students and taxonomists. Specimens were collected at altitudes between 270 m and 750 m above sea level using fine-meshed hand-nets and blacklight traps. The morphological species delimitation based on morphology was supplemented and congruent with mtDNA sequences which are the first DNA barcodes for the genus from Borneo. They were obtained in the field using a newly developed rapid and accurate MinION-based workflow. The inter – and intraspecific genetic distances and the problems regarding cryptic species delimitation are discussed.

http://www.zoobank.org/urn:lsid:zoobank.org:pub:4B1D0F3D-B303-46A5-86B4-C23454192327