University of Marburg

About: University of Marburg is a education organization based out in Marburg, Germany. It is known for research contribution in the topics: Population & Virus. The organization has 23195 authors who have published 42907 publications receiving 1506069 citations. The organization is also known as: Philipps University of Marburg & Philipps-Universität.

DNA Transfer from Organelles to the Nucleus: The Idiosyncratic Genetics of Endosymbiosis

Abstract: In eukaryotes, DNA is exchanged between endosymbiosis-derived compartments (mitochondria and chloroplasts) and the nucleus. Organelle-to-nucleus DNA transfer involves repair of double-stranded breaks by nonhomologous end-joining, and resulted during early organelle evolution in massive relocation of organelle genes to the nucleus. A large fraction of the products of the nuclear genes so acquired are retargeted to their ancestral compartment; many others now function in new subcellular locations. Almost all present-day nuclear transfers of mitochondrial or plastid DNA give rise to noncoding sequences, dubbed nuclear mitochondrial DNAs (NUMTs) and nuclear plastid DNAs (NUPTs). Some of these sequences were recruited as exons, thus introducing new coding sequences into preexisting nuclear genes by a novel mechanism. In organisms derived from secondary or tertiary endosymbiosis, serial gene transfers involving nucleus-to-nucleus migration of DNA have also occurred. Intercompartmental DNA transfer therefore rep...

The yeast frataxin homolog Yfh1p plays a specific role in the maturation of cellular Fe/S proteins

Abstract: The mitochondrial matrix protein frataxin is depleted in patients with Friedreich's ataxia, the most common autosomal recessive ataxia While frataxin is important for intracellular iron homeostasis, its exact cellular role is unknown Deletion of the yeast frataxin homolog YFH1 yields mutants ((Delta)yfh1) that, depending on the genetic background, display various degrees of phenotypic defects This renders it difficult to distinguish primary (early) from secondary (late) consequences of Yfh1p deficiency We have constructed a yeast strain (Gal-YFH1) that carries the YFH1 gene under the control of a galactose-regulated promoter Yfh1p-deficient Gal-YFH1 cells are far less sensitive to oxidative stress than (Delta)yfh1 mutants, maintain mitochondrial DNA, and synthesize heme at wild-type rates Yfh1p depletion causes a strong reduction in the assembly of mitochondrial Fe/S proteins both in vivo and in detergent extracts of mitochondria Impaired Fe/S protein biogenesis explains the respiratory deficiency of Gal-YFH1 cells Furthermore, Yfh1p-depleted Gal-YFH1 cells show decreased maturation of cytosolic Fe/S proteins and accumulation of mitochondrial iron This latter phenotype is common for defects in cytosolic Fe/S protein assembly Together, our data demonstrate a specific role of frataxin in the biosynthesis of cellular Fe/S proteins and exclude most of the previously suggested functions Friedreich's ataxia may therefore represent a disorder caused by defects in Fe/S protein maturation

Noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy: results of the Marburg Cardiomyopathy Study.

Abstract: Background— Arrhythmia risk stratification with regard to prophylactic implantable cardioverter-defibrillator therapy is a completely unsolved issue in idiopathic dilated cardiomyopathy (IDC). Methods and Results— Arrhythmia risk stratification was performed prospectively in 343 patients with IDC, including analysis of left ventricular (LV) ejection fraction and size by echocardiography, signal-averaged ECG, arrhythmias on Holter ECG, QTc dispersion, heart rate variability, baroreflex sensitivity, and microvolt T-wave alternans. During 52±21 months of follow-up, major arrhythmic events, defined as sustained ventricular tachycardia, ventricular fibrillation, or sudden death, occurred in 46 patients (13%). On multivariate analysis, LV ejection fraction was the only significant arrhythmia risk predictor in patients with sinus rhythm, with a relative risk of 2.3 per 10% decrease of ejection fraction (95% CI, 1.5 to 3.3; P=0.0001). Nonsustained ventricular tachycardia on Holter was associated with a trend towa...

Nuclear Actin Network Assembly by Formins Regulates the SRF Coactivator MAL

Abstract: Formins are potent activators of actin filament assembly in the cytoplasm. In turn, cytoplasmic actin polymerization can promote release of actin from megakaryocytic acute leukemia (MAL) protein for serum response factor (SRF) transcriptional activity. We found that formins polymerized actin inside the mammalian nucleus to drive serum-dependent MAL-SRF activity. Serum stimulated rapid assembly of actin filaments within the nucleus in a formin-dependent manner. The endogenous formin mDia was regulated with an optogenetic tool, which allowed for photoreactive release of nuclear formin autoinhibition. Activated mDia promoted rapid and reversible nuclear actin network assembly, subsequent MAL nuclear accumulation, and SRF activity. Thus, a dynamic polymeric actin structure within the nucleus is part of the serum response.

Cell cycle regulation of the cyclin A, cdc25C and cdc2 genes is based on a common mechanism of transcriptional repression.

Abstract: The S/G2-specific transcription of the human cdc25C gene is due to the periodic occupation of a repressor element ('cell cycle-dependent element'; CDE) located in the region of the basal promoter. Protein binding to the major groove of the CDE in G0 and G1 results in a phase-specific repression of activated transcription. We now show that CDE-mediated repression is also the major principle underlying the periodic transcription of the human cyclin A and cdc2 genes. A single point mutation within the CDE results in a 10- to 20-fold deregulation in G0 and an almost complete loss of cell cycle regulation of all three genes. In addition, the cdc25C, cyclin A and cdc2 genes share an identical 5 bp region ('cell cycle genes homology region'; CHR) starting at an identical position, six nucleotides 3' to the CDE. Strikingly, mutation of the CHR region in each of the three promoters produces the same phenotype as the mutation of the CDE, i.e. a dramatic deregulation in G0. In agreement with these results, in vivo DMS footprinting showed the periodic occupation of the cyclin A CDE in the major groove, and of the CHR in the minor groove. Finally, all three genes bear conspicuous similarities in their upstream activating sequences (UAS). This applies in particular to the presence of NF-Y and Sp1 binding sites which, in the cdc25C gene, have been shown to be the targets of repression through the CDE.(ABSTRACT TRUNCATED AT 250 WORDS)