CDK targets Sae2 to control DNA-end resection and homologous recombination

DNA double-strand breaks (DSBs) are repaired by two principal mechanisms: non-homologous end-joining (NHEJ) and homologous recombination (HR). HR is the most accurate DSB repair mechanism but is generally restricted to the S and G2 phases of the cell cycle, when DNA has been replicated and a sister chromatid is available as a repair template. By contrast, NHEJ operates throughout the cell cycle but assumes most importance in G1 (refs 4, 6). The choice between repair pathways is governed by cyclin-dependent protein kinases (CDKs), with a major site of control being at the level of DSB resection, an event that is necessary for HR but not NHEJ, and which takes place most effectively in S and G2 (refs 2, 5). Here we establish that cell-cycle control of DSB resection in Saccharomyces cerevisiae results from the phosphorylation by CDK of an evolutionarily conserved motif in the Sae2 protein. We show that mutating Ser 267 of Sae2 to a non-phosphorylatable residue causes phenotypes comparable to those of a sae2Delta null mutant, including hypersensitivity to camptothecin, defective sporulation, reduced hairpin-induced recombination, severely impaired DNA-end processing and faulty assembly and disassembly of HR factors. Furthermore, a Sae2 mutation that mimics constitutive Ser 267 phosphorylation complements these phenotypes and overcomes the necessity of CDK activity for DSB resection. The Sae2 mutations also cause cell-cycle-stage specific hypersensitivity to DNA damage and affect the balance between HR and NHEJ. These findings therefore provide a mechanistic basis for cell-cycle control of DSB repair and highlight the importance of regulating DSB resection.     

Oxidative stress and impaired oligodendrocyte precursor cell differentiation in neurological disorders

Cellular and Molecular Life Sciences - Oligodendrocyte precursor cells (OPCs) account for 5% of the resident parenchymal central nervous system glial cells. OPCs are not only a back-up for the loss...     

Faunistic analysis of Cerambycidae (Insecta: Coleoptera) in an area of Atlantic Forest

The Atlantic Forest is considered a hotspot biome, one of the most diverse in the world. Currently, due to deforestation, only 22% of the original cover remains, and only 7.5% well preserved. Despite the global importance of this biome, it still lacks basic studies, e.g. primary inventories. Cerambycidae is one of the most diverse groups of beetles, with high ecological and economic importance. The aim of this work was to survey the longhorn beetles (Cerambycidae) in three fragments (Pacangê, Vila 5 and Pancada Grande) of Atlantic Forest within Reserva Ecológica da Michelin (southern Bahia State, Brazil). A total of 166 individuals belonging to 53 species were recorded, 15 of them new geographical records for the state, and one for Brazil. The Shannon index (H) shows Pacangê (H = 2.665) as the most diverse fragment, followed by Pancada Grande (H = 2.658) and Vila 5 (H = 2.565). The most abundant species were Nyssodrysina lignaria (38 specimens collected), followed by Compsibidion vanum (31 specimens). One hundred and ten specimens were captured in Malaise traps, while in light traps only 56 specimens were caught; however, the richness and consequently the diversity in light traps was higher. This is one of the few studies carried out in Atlantic Forest surveying longhorn beetles, and provides primary data on these taxa, to help develop conservation policies for this threatened biome.     

Prediction of central nervous system embryonal tumour outcome based on gene expression.

Embryonal tumours of the central nervous system (CNS) represent a heterogeneous group of tumours about which little is known biologically, and whose diagnosis, on the basis of morphologic appearance alone, is controversial. Medulloblastomas, for example, are the most common malignant brain tumour of childhood, but their pathogenesis is unknown, their relationship to other embryonal CNS tumours is debated, and patients' response to therapy is difficult to predict. We approached these problems by developing a classification system based on DNA microarray gene expression data derived from 99 patient samples. Here we demonstrate that medulloblastomas are molecularly distinct from other brain tumours including primitive neuroectodermal tumours (PNETs), atypical teratoid/rhabdoid tumours (AT/RTs) and malignant gliomas. Previously unrecognized evidence supporting the derivation of medulloblastomas from cerebellar granule cells through activation of the Sonic Hedgehog (SHH) pathway was also revealed. We show further that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumours at diagnosis.     

RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone.

Neurotransmitters are released by synaptic vesicle fusion at the active zone. The active zone of a synapse mediates Ca2+-triggered neurotransmitter release, and integrates presynaptic signals in regulating this release. Much is known about the structure of active zones and synaptic vesicles, but the functional relation between their components is poorly understood. Here we show that RIM1alpha, an active zone protein that was identified as a putative effector for the synaptic vesicle protein Rab3A, interacts with several active zone molecules, including Munc13-1 (ref. 6) and alpha-liprins, to form a protein scaffold in the presynaptic nerve terminal. Abolishing the expression of RIM1alpha in mice shows that RIM1alpha is essential for maintaining normal probability of neurotransmitter release, and for regulating release during short-term synaptic plasticity. These data indicate that RIM1alpha has a central function in integrating active zone proteins and synaptic vesicles into a molecular scaffold that controls neurotransmitter release.     

The eagle and the starlings: Galileo’s argument for the autonomy of science—how pertinent is it today?

After Galileo’s argument for the autonomy of science is analysed and adapted to take into account later developments of scientific practices, we conclude that, in the final analysis, it is not compelling. Nevertheless, Galileo’s argument still provides a useful point of reference, for aspects of it can be interpreted to anticipate central components of the often acclaimed ideal of science as value free, so that appraising it contributes to the larger purpose of exploring how well that ideal stands up today. Finally, we will argue that residue from Galileo’s struggle with the Church remains with us, making it difficult to identify the conditions that would need to be put into place today for any robust sense of the autonomy of science to be defensible.     

Eisosomes mark static sites of endocytosis

Endocytosis functions to recycle plasma membrane components, to regulate cell-surface expression of signalling receptors and to internalize nutrients in all eukaryotic cells. Internalization of proteins, lipids and other cargo can occur by one of several pathways that have different, but often overlapping, molecular requirements. To mediate endocytosis, effectors assemble transiently underneath the plasma membrane, carry out the mechanics of membrane deformation, cargo selection and vesicle internalization, and then disassemble. The mechanism by which endocytosis initiates at particular locations on the plasma membrane has remained unknown. Sites of endocytosis might be formed randomly, induced by stochastic protein and/or lipid clustering. Alternatively, endocytosis might initiate at specific locations. Here we describe large immobile protein assemblies at the plasma membrane in the yeast Saccharomyces cerevisiae that mark endocytic sites. These structures, termed eisosomes (from the Greek 'eis', meaning into or portal, and 'soma', meaning body), are composed primarily of two cytoplasmic proteins, Pil1 and Lsp1. A plasma membrane protein, Sur7, localizes to eisosomes. These structures colocalize with sites of protein and lipid endocytosis, and their components genetically interact with known endocytic effectors. Loss of Pil1 leads to clustering of eisosome remnants and redirects endocytosis and endocytic effector proteins to these clusters.     

Early maize agriculture and interzonal interaction in southern Peru

Over the past decade, increasing attention to the recovery and identification of plant microfossil remains from archaeological sites located in lowland South America has significantly increased knowledge of pre-Columbian plant domestication and crop plant dispersals in tropical forests and other regions. Along the Andean mountain chain, however, the chronology and trajectory of plant domestication are still poorly understood for both important indigenous staple crops such as the potato (Solanum sp.) and others exogenous to the region, for example, maize (Zea mays). Here we report the analyses of plant microremains from a late preceramic house (3,431 +/- 45 to 3,745 +/- 65 14C bp or approximately 3,600 to 4,000 calibrated years bp) in the highland southern Peruvian site of Waynuna. Our results extend the record of maize by at least a millennium in the southern Andes, show on-site processing of maize into flour, provide direct evidence for the deliberate movement of plant foods by humans from the tropical forest to the highlands, and confirm the potential of plant microfossil analysis in understanding ancient plant use and migration in this region.     

A new hominid from the Upper Miocene of Chad,Central Africa

The search for the earliest fossil evidence of the human lineage has been concentrated in East Africa. Here we report the discovery of six hominid specimens from Chad, central Africa, 2,500 km from the East African Rift Valley. The fossils include a nearly complete cranium and fragmentary lower jaws. The associated fauna suggest the fossils are between 6 and 7 million years old. The fossils display a unique mosaic of primitive and derived characters, and constitute a new genus and species of hominid. The distance from the Rift Valley, and the great antiquity of the fossils, suggest that the earliest members of the hominid clade were more widely distributed than has been thought, and that the divergence between the human and chimpanzee lineages was earlier than indicated by most molecular studies.