Molecular genetic diversity of the Turkish national hazelnut collection and selection of a core set

European hazelnut (Corylus avellana L.) is an economically and nutritionally important nut crop with wild and cultivated populations found throughout Europe and in parts of Asia. This study examined the molecular genetic diversity and population structure of 402 genotypes including 143 wild individuals, 239 landraces, and 20 cultivars from the Turkish national hazelnut collection using simple sequence repeat (SSR) markers. A total of 30 SSR markers yielded 407 polymorphic fragments. Diversity analysis of the Turkish hazelnut genotypes indicated that they fell into three subpopulations according to ad hoc statistics and neighbor-joining algorithm. Although all cultivars clustered together, they overlapped with the wild accessions and landraces. Thus, the dendrogram, principal coordinate, and population structure analyses suggest that they share the same gene pool. A total of 78 accessions were selected as a core set to encompass the molecular genetic and morphological diversity present in the national collection. This core set should have priority in preservation efforts and in trait characterization.     

Glycosphingolipids and cell death

Sphingolipids have been implicated in various cellular processes including growth, cell-cell or ligand-receptor interactions, and differentiation. In addition to their importance as reservoirs of metabolites with important signaling properties, sphingolipids also help provide structural order to plasma membrane lipids and proteins within the bilayer. Glycosylated sphingolipids, and sphingomyelin in particular, are involved in the formation of lipid rafts. Although it is well accepted that ceramide, the backbone of all sphingolipids, plays a critical role in apoptosis, less is known about the biological functions of glycosphingolipids. This review summarizes current knowledge of the involvement of glycosphingolipids in cell death and in other pathological processes and diseases. Published in 2004. This revised version was published online in August 2006 with corrections to the Cover Date.     

SETDB1, HP1 and SUV39 promote repositioning of 53BP1 to extend resection during homologous recombination in G2 cells

Recent studies have shown that homologous recombination (HR) requires chromatin repression as well as relaxation at DNA double strand breaks (DSBs). HP1 and SUV39H1/2 are repressive factors essential for HR. Here, we identify SETDB1 as an additional compacting factor promoting HR. Depletion of HP1, SUV39, SETDB1 or BRCA1 confer identical phenotypes. The repressive factors, like BRCA1, are dispensable for the initiation of resection but promote the extension step causing diminished RPA or RAD51 foci and HR in irradiated G2 cells. Depletion of the compacting factors does not inhibit BRCA1 recruitment but at 8 h post IR, BRCA1 foci are smaller and aberrantly positioned compared to control cells. BRCA1 promotes 53BP1 repositioning to the periphery of enlarged foci and formation of a devoid core with BRCA1 becoming enlarged and localized internally to 53BP1. Depletion of the compacting factors precludes these changes at irradiation-induced foci. Thus, the repressive factors are required for BRCA1 function in promoting the repositioning of 53BP1 during HR. Additionally, depletion of these repressive factors in undamaged cells causes diminished sister chromatid association at centromeric sequences. We propose a model for how these findings may be functionally linked.     

Effect of stagnant hypoxia on acid ribonuclease activity in the rat prosencephalon during ontogenesis.

In the rat prosencephalon it proved possible to differentiate lysosomal ribonuclease from alkaline ribonuclease activity, which could be detected only in the presence of p-chlormercuribenzoate. Acid RNase activity related to the amount of protein in the prosencephalon fell during ontogenesis. It was not significantly affected by four hours' stagnant hypoxia induced by ligation of both carotids. Its release from the lysosomes rose, however (when isotonic homogenates were spun at 20,000 g, acid ribonuclease activity in the supernatants was elevated). The absence of correlation between this activation and the degree of maturity of the nervous tissue refutes the hypothesis that regulation of this enzyme is per se responsible for the known changes induced by hypoxia in the RNA content of the prosencephalon of rats of different ages. On the contrary, the results indirectly support studies which demonstrate changes in the extent of RNA synthesis after hypoxia.     

TDP1 deficiency sensitizes human cells to base damage via distinct topoisomerase I and PARP mechanisms with potential applications for cancer therapy

Base damage and topoisomerase I (Top1)-linked DNA breaks are abundant forms of endogenous DNA breakage, contributing to hereditary ataxia and underlying the cytotoxicity of a wide range of anti-cancer agents. Despite their frequency, the overlapping mechanisms that repair these forms of DNA breakage are largely unknown. Here, we report that depletion of Tyrosyl DNA phosphodiesterase 1 (TDP1) sensitizes human cells to alkylation damage and the additional depletion of apurinic/apyrimidinic endonuclease I (APE1) confers hypersensitivity above that observed for TDP1 or APE1 depletion alone. Quantification of DNA breaks and clonogenic survival assays confirm a role for TDP1 in response to base damage, independently of APE1. The hypersensitivity to alkylation damage is partly restored by depletion of Top1, illustrating that alkylating agents can trigger cytotoxic Top1-breaks. Although inhibition of PARP activity does not sensitize TDP1-deficient cells to Top1 poisons, it confers increased sensitivity to alkylation damage, highlighting partially overlapping roles for PARP and TDP1 in response to genotoxic challenge. Finally, we demonstrate that cancer cells in which TDP1 is inherently deficient are hypersensitive to alkylation damage and that TDP1 depletion sensitizes glioblastoma-resistant cancer cells to the alkylating agent temozolomide.     

Annexin A6-regulator of the EGFR/Ras signalling pathway and cholesterol homeostasis

Annexin A6 (AnxA6) belongs to the highly conserved annexin protein family. Like other annexins, the function of AnxA6 is linked to its ability to bind phospholipids in a Ca²⁺-dependent manner, thereby interacting with cellular membranes in a dynamic, reversible and regulated fashion. Upon cell activation, AnxA6 is recruited to the plasma membrane, endosomes and caveolae/membrane rafts to interact with signalling proteins, the endocytic machinery and actin cytoskeleton to inhibit epidermal growth factor receptor and Ras signalling. In addition, AnxA6 associates with late endosomes to regulate cholesterol export leading to reduced cytoplasmic phospholipase A2 activity and caveolae formation. Accordingly, AnxA6 may function as an organizer of membrane domains (i) to create a scaffold for the formation of multifactorial signalling complexes, (ii) to regulate transient membrane–actin interactions during endocytic transport, and (iii) to modulate intracellular cholesterol homeostasis. Altogether, this will regulate critical physiological processes including proliferation, differentiation, inflammation and cell migration.