The double-stranded DNA-binding proteins TEBP-1 and TEBP-2 form a telomeric complex with POT-1

Telomeres are bound by dedicated proteins, which protect them from DNA damage and regulate telomere length homeostasis. In the nematode Caenorhabditis elegans, a comprehensive understanding of the proteins interacting with the telomere sequence is lacking. Here, we harnessed a quantitative proteomics approach to identify TEBP-1 and TEBP-2, two paralogs expressed in the germline and embryogenesis that associate to telomeres in vitro and in vivo. tebp-1 and tebp-2 mutants display strikingly distinct phenotypes: tebp-1 mutants have longer telomeres than wild-type animals, while tebp-2 mutants display shorter telomeres and a Mortal Germline. Notably, tebp-1;tebp-2 double mutant animals have synthetic sterility, with germlines showing signs of severe mitotic and meiotic arrest. Furthermore, we show that POT-1 forms a telomeric complex with TEBP-1 and TEBP-2, which bridges TEBP-1/-2 with POT-2/MRT-1. These results provide insights into the composition and organization of a telomeric protein complex in C. elegans

Characterization of the mechanism by which the RB/E2F pathway controls expression of the cancer genomic DNA deaminase APOBEC3B

APOBEC3B (A3B)-catalyzed DNA cytosine deamination contributes to the overall mutational landscape in breast cancer. Molecular mechanisms responsible for A3B upregulation in cancer are poorly understood. Here we show that a single E2F cis-element mediates repression in normal cells and that expression is activated by its mutational disruption in a reporter construct or the endogenous A3B gene. The same E2F site is required for A3B induction by polyomavirus T antigen indicating a shared molecular mechanism. Proteomic and biochemical experiments demonstrate the binding of wildtype but not mutant E2F promoters by repressive PRC1.6/E2F6 and DREAM/E2F4 complexes. Knockdown and overexpression studies confirm the involvement of these repressive complexes in regulating A3B expression. Altogether, these studies demonstrate that A3B expression is suppressed in normal cells by repressive E2F complexes and that viral or mutational disruption of this regulatory network triggers overexpression in breast cancer and provides fuel for tumor evolution

The double-stranded DNA-binding proteins TEBP-1 and TEBP-2 form a telomeric complex with POT-1.

Telomeres are bound by dedicated proteins, which protect them from DNA damage and regulate telomere length homeostasis. In the nematode Caenorhabditis elegans, a comprehensive understanding of the proteins interacting with the telomere sequence is lacking. Here, we harnessed a quantitative proteomics approach to identify TEBP-1 and TEBP-2, two paralogs expressed in the germline and embryogenesis that associate to telomeres in vitro and in vivo. tebp-1 and tebp-2 mutants display strikingly distinct phenotypes: tebp-1 mutants have longer telomeres than wild-type animals, while tebp-2 mutants display shorter telomeres and a Mortal Germline. Notably, tebp-1;tebp-2 double mutant animals have synthetic sterility, with germlines showing signs of severe mitotic and meiotic arrest. Furthermore, we show that POT-1 forms a telomeric complex with TEBP-1 and TEBP-2, which bridges TEBP-1/-2 with POT-2/MRT-1. These results provide insights into the composition and organization of a telomeric protein complex in C. elegans

Telomeres are shorter in myocardial infarction patients compared to healthy subjects: correlation with environmental risk factors

Shorter telomeres have been reported in premature myocardial infarction (MI) patients. Our work aimed at confirming the association of shorter telomere with MI in two case–control studies and in familial hypercholesterolemia (FH) patients with coronary heart disease (CHD). The HIFMECH study compared 598 white male patients (<60 years) who survived a first MI and 653 age-matched controls from North and South Europe. Additionally, from the UK, 413 coronary artery bypass graft (CABG) patients and two groups of 367 and 94 FH patients, of whom 145 and 17 respectively had premature CHD, were recruited. Leukocyte telomere length (LTL) was measured using a real-time polymerase chain reaction-based method. In HIFMECH, LTL was significantly shorter in subjects from the North (7.99 kb, SD 4.51) compared to the South (8.27 kb, SD 4.14; p = 0.02) and in cases (7.85 kb, SD 4.01) compared to controls (8.04 kb, SD 4.46; p = 0.04). In the CABG study, LTL was significantly shorter (6.89 kb, SD 4.14) compared to the HIFMECH UK controls (7.53, SD 5.29; p = 0.007). In both samples of FH patients, LTL was shorter in those with CHD (overall 8.68 kb, SD 4.65) compared to the non-CHD subjects (9.23 kb, SD 4.83; p = 0.012). Apart from a consistent negative correlation with age, LTL was not associated across studies with any measured CHD risk factors. The present data confirms that subjects with CHD have shorter telomeres than controls and extends this to those with monogenic and polygenic forms of CHD

Sex Differences in Sand Lizard Telomere Inheritance: Paternal Epigenetic Effects Increases Telomere Heritability and Offspring Survival

To date, the only estimate of the heritability of telomere length in wild populations comes from humans. Thus, there is a need for analysis of natural populations with respect to how telomeres evolve.Here, we show that telomere length is heritable in free-ranging sand lizards, Lacerta agilis. More importantly, heritability estimates analysed within, and contrasted between, the sexes are markedly different; son-sire heritability is much higher relative to daughter-dam heritability. We assess the effect of paternal age on Telomere Length (TL) and show that in this species, paternal age at conception is the best predictor of TL in sons. Neither paternal age per se at blood sampling for telomere screening, nor corresponding age in sons impact TL in sons. Processes maintaining telomere length are also associated with negative fitness effects, most notably by increasing the risk of cancer and show variation across different categories of individuals (e.g. males vs. females). We therefore tested whether TL influences offspring survival in their first year of life. Indeed such effects were present and independent of sex-biased offspring mortality and offspring malformations.TL show differences in sex-specific heritability with implications for differences between the sexes with respect to ongoing telomere selection. Paternal age influences the length of telomeres in sons and longer telomeres enhance offspring survival

Wissensmanagement von Altdokumenten aus Forschung, Verwaltung und Betrieb: Schlussbericht.

Der Niedersächsische Landtag empfahl der Landesregierung in seiner Beschlussempfehlung vom 07.11.2012 (Drs. 16/5386), den Aktenbestand nach Abschluss der Arbeiten des 21. Parlamentarischen Untersuchungsausschusses (PUA) dem Niedersächsischen Landesarchiv (NLA) zu übergeben und dort an zentraler Stelle der Öffentlichkeit bzw. für Forschungszwecke zur Verfügung zu stellen. &nbsp; Darüber hinaus würde der Landtag es sehr begrüßen, wenn das Bundesministerium für Bildung und Forschung aus seiner politisch-historischen Verantwortung als langjähriger Zuwendungsgeber für die Schachtanlage Asse II mit dazu beitragen könnte, die Erkenntnisse aus sämtlichen Akten des Untersuchungsausschusses zusammenzutragen und aufzubereiten. &nbsp; Im Zuge dieser Unterstützung hat das HMGU im Rahmen des Projektes ca. 950.000 Seiten, die für den 21. PUA zusammengetragen wurden, gescannt und mit Hilfe des Programmpaketes Topic Analyst der Firma CID analysiert. Für die Analyse mussten die Scans mit einer OCR bearbeitet werden. Um die Qualität der OCR zu verbessern, entwickelte die Universität Leipzig geeignete Tools. &nbsp; Mit dem Projekt wurde erstmals ein Datenpool aus Altakten computergestützt inhaltlich erfasst und ausgewertet. Auf Grundlage der Erkenntnisse wurden Synthesen erstellt, aus denen Empfehlungen für eine zukünftige Endlagersuche abgeleitet werden konnten. Im Rahmen dieser Arbeiten wurden die auf der Schachtanlage Asse II durchgeführten Forschungsvorhaben, z. B. bezüglich Geologie, Gebirgsmechanik, Gebirgsbeobachtungen, Geophysik, Lauge, Strahlenschutz und Sicherheitsbetrachtungen, zusammenfassend dargestellt und können für eine zukünftige Endlagersuche als Grundlage genutzt werden. &nbsp; Es stellte sich heraus, dass bei der Bewertung und Interpretation von Gutachten durch Fachleute individuelle Maßstäbe angelegt werden. Aus dieser Erkenntnis heraus wurden linguistische Analysen ausgewählter Gutachten manuell erstellt. Die Ergebnisse stellen eine sehr gute Grundlage für eine noch zu entwickelnde automatisierte linguistische Analyse von Gutachten dar. &nbsp; Die Analyse großer Datenmengen mit dem Programmpaket Topic Analyst ist für viele Bereiche anwendbar. Zu nennen sind insbesondere Untersuchungsausschüsse oder wissenschaftliche Datenbanken. &nbsp; Im Rahmen des Projektes wurden insgesamt 2228 Gutachten, Berichte und wissenschaftliche Arbeiten identifiziert, von denen 1767 beschafft, gescannt und archiviert werden konnten. 461 Unterlagen sind bei anderen Einrichtungen oder Bibliotheken vorhanden