A role for chromatin remodellers in replication of damaged DNA

In eukaryotic cells, replication past damaged sites in DNA is regulated by the ubiquitination of proliferating cell nuclear antigen (PCNA). Little is known about how this process is affected by chromatin structure. There are two isoforms of the Remodels the Structure of Chromatin (RSC) remodelling complex in yeast. We show that deletion of RSC2 results in a dramatic reduction in the level of PCNA ubiquitination after DNA-damaging treatments, whereas no such effect was observed after deletion of RSC1. Similarly, depletion of the BAF180 component of the corresponding PBAF (Polybromo BRG1 (Brahma-Related Gene 1) Associated Factor) complex in human cells led to a similar reduction in PCNA ubiquitination. Remarkably, we found that depletion of BAF180 resulted after UV-irradiation, in a reduction not only of ubiquitinated PCNA but also of chromatin-associated unmodified PCNA and Rad18 (the E3 ligase that ubiquitinates PCNA). This was accompanied by a modest decrease in fork progression. We propose a model to account for these findings that postulates an involvement of PBAF in repriming of replication downstream from replication forks blocked at sites of DNA damage. In support of this model, chromatin immunoprecipitation data show that the RSC complex in yeast is present in the vicinity of the replication forks, and by extrapolation, this is also likely to be the case for the PBAF complex in human cells

Identification of the proteins, including MAGEG1, that make up the human SMC5-6 protein complex

The SMC protein complexes play important roles in chromosome dynamics. The function of the SMC5-6 complex remains unclear, though it is involved in resolution of different DNA structures by recombination. We have now identified and characterized the four non-SMC components of the human complex and in particular demonstrated that the MAGEG1 protein is part of this complex. MAGE proteins play important but as yet undefined roles in carcinogenesis, apoptosis, and brain development. We show that, with the exception of the SUMO ligase hMMS21/hNSE2, depletion of any of the components results in degradation of all the other components. Depletion also confers sensitivity to methyl methanesulfonate. Several of the components are modified by sumoylation and ubiquitination

Test Preparation in Figural Matrices Tests: Focus on the Difficult Rules

It is well documented that training the rules employed in figural matrices tests enhances test performance. Previous studies only compare experimental conditions in which all or no rules were trained and therefore ignore the particular influence of knowledge about the easy and difficult rules. With the current study, we wanted to provide some first insights into this topic. Respondents were assigned to four groups that received training for no rules, only the easy rules, only the difficult rules, or for all rules. The results show that a training only for the difficult rules was more effective than the other trainings. This applies also to performance in the easy rules that were actually not part of the training. A possible explanation for this finding is a facilitation of the solution process that is primarily driven by knowledge about the difficult rules. In conclusion, our results demonstrate that taking differences between the rules into account may provide a deeper understanding of the effects of trainings for figural matrices test

Parameter space mapping of InAs nanowire crystal structure

Crystal structure and defects have been shown to have a strong impact on III-Vnanowire properties. Recently, it was demonstrated that the issue of random stacking and polytypism in semiconductornanowires can often be controlled using accessible growth parameters (such as temperature, diameter, and V/III ratio). In addition, it has been shown that crystal phase can be tuned selectively between cubic zinc blende and hexagonal wurtzite within individual nanowires of III-V materials such as InAs. In order for such results to be generally applied to different growth setups, it is necessary to fully explore and understand the trends governing crystal phase dependencies on all accessible growth parameters, including how they relate to each other. In this study, the authors have systematically investigated the influence of temperature, diameter, V/III ratio, and total mass flow on the crystal structure of InAsnanowiresgrown by metal-organic vapor phase epitaxy over a broad parameter range. The authors observed that each of these accessible parameters can affect the resulting crystal structure, and that the trends for each parameter are affected by the magnitude of the others. The authors also noted that most of the parameter dependencies are nonlinear and, in fact, exhibit threshold values at which structure changes discontinuously. By optimizing each of the growth parameters, it is shown that pure ZB or pure WZ phase can be achieved for several different sets of growth conditions. The roles of nucleation kinetics, thermodynamics, and precursor chemistry are also discussed to compare the results to current nanowiregrowth models. The results in this work should facilitate comparison of data and transfer of knowledge between different growth systems and techniques, which, in turn, should lead to greater understanding of polytypism in nanowires and greater control and freedom in nanowire crystal phase engineering.This work was supported by the Nanometer Structure Consortium at Lund University nmC@LU, the Swedish Foundation for Strategic Research SSF, the Swedish Research Council VR, and the Knut and Alice Wallenberg Foundation

University for the Creative Arts staff research 2011

This publication brings together a selection of the University’s current research. The contributions foreground areas of research strength including still and moving image research, applied arts and crafts, as well as emerging fields of investigations such as design and architecture. It also maps thematic concerns across disciplinary areas that focus on models and processes of creative practice, value formations and processes of identification through art and artefacts as well as cross-cultural connectivity. Dr. Seymour Roworth-Stoke

Interactions between the Nse3 and Nse4 Components of the SMC5-6 Complex Identify Evolutionarily Conserved Interactions between MAGE and EID Families

The SMC5-6 protein complex is involved in the cellular response to DNA damage. It is composed of 6-8 polypeptides, of which Nse1, Nse3 and Nse4 form a tight sub-complex. MAGEG1, the mammalian ortholog of Nse3, is the founding member of the MAGE (melanoma-associated antigen) protein family and Nse4 is related to the EID (E1A-like inhibitor of differentiation) family of transcriptional repressors.Using site-directed mutagenesis, protein-protein interaction analyses and molecular modelling, we have identified a conserved hydrophobic surface on the C-terminal domain of Nse3 that interacts with Nse4 and identified residues in its N-terminal domain that are essential for interaction with Nse1. We show that these interactions are conserved in the human orthologs. Furthermore, interaction of MAGEG1, the mammalian ortholog of Nse3, with NSE4b, one of the mammalian orthologs of Nse4, results in transcriptional co-activation of the nuclear receptor, steroidogenic factor 1 (SF1). In an examination of the evolutionary conservation of the Nse3-Nse4 interactions, we find that several MAGE proteins can interact with at least one of the NSE4/EID proteins.We have found that, despite the evolutionary diversification of the MAGE family, the characteristic hydrophobic surface shared by all MAGE proteins from yeast to humans mediates its binding to NSE4/EID proteins. Our work provides new insights into the interactions, evolution and functions of the enigmatic MAGE proteins