The nuclear envelope: emerging roles in development and disease

The chromosomes of eukaryotic cells are separated from the cytoplasm by the nuclear envelope. The nuclear envelope includes two riveted membranes, plus embedded pore complexes that mediate nuclear import and export. In this sense, the nuclear envelope is truly a border zone. However, the envelope also links directly to chromosomes, and anchors two major infrastructures--the nuclear lamina and Tpr filaments--to the nuclear perimeter. Proteins of the nuclear envelope mediate a variety of fundamental activities, including DNA replication, gene expression and silencing, chromatin organization, cell division, apoptosis, sperm nuclear remodeling, the behavior of pronuclei, cell fate determination, nuclear migration and cell polarity. Furthermore, mutations in nuclear lamins and lamin-binding proteins cause tissue-specific inherited diseases. This special issue of Cell and Molecular Life Sciences is devoted to recent major advances in the characterization of nuclear envelope proteins and their roles. We offer here an overview of the topics covered in this issue of CMLS, and also discuss the emerging recognition that the nuclear envelope is an organelle critical for a wide range of genetic and developmental activity in multicellular organisms.     

The Ku complex: recent advances and emerging roles outside of non-homologous end-joining

Cellular and Molecular Life Sciences - Since its discovery in 1981, the Ku complex has been extensively studied under multiple cellular contexts, with most work focusing on Ku in terms of its...     

Regulatory mechanisms of RNA function: emerging roles of DNA repair enzymes

The acquisition of an appropriate set of chemical modifications is required in order to establish correct structure of RNA molecules, and essential for their function. Modification of RNA bases affects RNA maturation, RNA processing, RNA quality control, and protein translation. Some RNA modifications are directly involved in the regulation of these processes. RNA epigenetics is emerging as a mechanism to achieve dynamic regulation of RNA function. Other modifications may prevent or be a signal for degradation. All types of RNA species are subject to processing or degradation, and numerous cellular mechanisms are involved. Unexpectedly, several studies during the last decade have established a connection between DNA and RNA surveillance mechanisms in eukaryotes. Several proteins that respond to DNA damage, either to process or to signal the presence of damaged DNA, have been shown to participate in RNA quality control, turnover or processing. Some enzymes that repair DNA damage may also process modified RNA substrates. In this review, we give an overview of the DNA repair proteins that function in RNA metabolism. We also discuss the roles of two base excision repair enzymes, SMUG1 and APE1, in RNA quality control.     

The emerging roles of ribosomal histidyl hydroxylases in cell biology,physiology and disease

Hydroxylation is a novel protein modification catalyzed by a family of oxygenases that depend on fundamental nutrients and metabolites for activity. Protein hydroxylases have been implicated in a variety of key cellular processes that play important roles in both normal homeostasis and pathogenesis. Here, in this review, we summarize the current literature on a highly conserved sub-family of oxygenases that catalyze protein histidyl hydroxylation. We discuss the evidence supporting the biochemical assignment of these emerging enzymes as ribosomal protein hydroxylases, and provide an overview of their role in immunology, bone development, and cancer.     

Altered wound healing in X-irradiated rats: The effect of bone marrow shielding

Zusammenfassung Weibliche, 10–12 Wochen alte Ratten erhielten eine einmalige Ganzkörperbestrahlung (250 kV_Sch; 800 R freie Luft); bei einem Teil der Tiere waren das Becken und die Hinterbeine durch Bleizylinder abgeschirmt. Vier Tage später wurde der Hälfte der Tiere eine Wunde beigebracht. Sowohl bei den verwundeten wie nichtverwundeten Tieren führte Abschirmung des Knochenmarks zu starker Sterblichkeitsminderung. Die fast normale Schliessungsgeschwindigkeit der Wunde scheint vom intakten Knochenmark abhängig.     

Sex chromosome inactivation in germ cells: emerging roles of DNA damage response pathways

Sex chromosome inactivation in male germ cells is a paradigm of epigenetic programming during sexual reproduction. Recent progress has revealed the underlying mechanisms of sex chromosome inactivation in male meiosis. The trigger of chromosome-wide silencing is activation of the DNA damage response (DDR) pathway, which is centered on the mediator of DNA damage checkpoint 1 (MDC1), a binding partner of phosphorylated histone H2AX (γH2AX). This DDR pathway shares features with the somatic DDR pathway recognizing DNA replication stress in the S phase. Additionally, it is likely to be distinct from the DDR pathway that recognizes meiosis-specific double-strand breaks. This review article extensively discusses the underlying mechanism of sex chromosome inactivation.     

The emerging roles for the chromatin structure regulators CTCF and cohesin in neurodevelopment and behavior

Recent genetic and technological advances have determined a role for chromatin structure in neurodevelopment. In particular, compounding evidence has established roles for CTCF and cohesin, two elements that are central in the establishment of chromatin structure, in proper neurodevelopment and in regulation of behavior. Genetic aberrations in CTCF, and in subunits of the cohesin complex, have been associated with neurodevelopmental disorders in human genetic studies, and subsequent animal studies have established definitive, although sometime opposing roles, for these factors in neurodevelopment and behavior. Considering the centrality of these factors in cellular processes in general, the mechanisms through which dysregulation of CTCF and cohesin leads specifically to neurological phenotypes is intriguing, although poorly understood. The connection between CTCF, cohesin, chromatin structure, and behavior is likely to be one of the next frontiers in our understanding of the development of behavior in general, and neurodevelopmental disorders in particular.     

The PAS-domain kinase PASKIN: a new sensor in energy homeostasis

The PAS domain kinase PASKIN, also termed PAS kinase or PASK, is an evolutionarily conserved potential sensor kinase related to the heme-based oxygen sensors of nitrogen-fixing bacteria. In yeast, the two PASKIN homologs link energy flux and protein synthesis following specific stress conditions. In mammals, PASKIN may regulate glycogen synthesis and protein translation. Paskin knock-out mice do not show any phenotype under standard animal husbandry conditions. Interestingly, these mice seem to be protected from the symptoms of the metabolic syndrome when fed a high-fat diet. Energy turnover might be increased in specific PASKIN-deficient cell types under distinct environmental conditions. According to the current model, binding of a putative ligand to the PAS domain disinhibits the kinase domain and activates PASKIN auto- and target phosphorylation. Future research needs to be conducted to elucidate the nature of the putative ligand and the molecular mechanisms of downstream signalling by PASKIN. Received 2 November 2008; received after revision 10 December 2008; accepted 5 January 2009     

The predictability of stock market volatility in emerging economies: Relative roles of local,regional, and global business cycles

This paper explores the role of business cycle proxies, measured by the output gap at the global, regional, and local levels, as potential predictors of stock market volatility in the emerging BRICS nations. We observe that the emerging BRICS nations display a rather heterogeneous pattern when it comes to the relative role of idiosyncratic factors as a predictor of stock market volatility. While domestic output gap is found to capture significant predictive information for India and China particularly, the business cycles associated with emerging economies and the world in general are strongly important for the BRIC countries and weakly for South Africa, especially in the postglobal financial crisis era. The findings suggest that despite the increase in the financial integration of world capital markets, emerging economies can still bear significant exposures to idiosyncratic risk factors, an issue of high importance for the profitability of global diversification strategies.     

The early response of59Fe incorporation in the bone marrow of irradiated rats

Summary The change in radioiron uptake in selected bone marrow samples in irradiated rats is representative of the total skeletal uptake only if the baseline or radioresistant uptake has been subtracted.This paper is based on work performed under contract with the US Energy Research and Development Administration at the University of Rochester Biomedical and Environmental Research Project, and has been assigned Report No. UR-3490-949.     

Histidine decarboxylase in the bone marrow of the rat

Résumé Dans l'étude ci-dessus la formation d'histamine dans la moelle osseuse du rat adulte a été attribuée à une enzyme identique ou semblable à la décarboxylase d'histidine du rat foetal. Par conséquence, l'enzyme de la moelle osseuse diffère de l'enzyme qui, étant présente dans l'écorce rénale des animaux adultes, forme l'histamine.     

Androgens and erythropoiesis in bone marrow. II. Effect of testosterone propionate on59Fe concentration in erythrocytes and bone marrow

Résumé L'augmentation d'incorporation de⁵⁹Fe dans les globules rouge de rats auxquels on a donné du testosterone propionate est évidente dans la circulation périphérique du sang, 24 h après l'injection du⁵⁹Fe. Le rapport entre cette donnée et le temps de transfert des erythroblastes dans la moelle osseuse montre que les androgènes stimulent la maturation de normoblastes basophiliques et polychromatophiliques, plutôt que l'érythropoietine.

---

---

Supported by contract No. PH-43-65-6, General Laboratories and Clinics, National Cancer Institute, Public Health Service.