The Possible Crosstalk of MOB2 With NDR1/2 Kinases in Cell Cycle and DNA Damage Signaling

This article is the authors’ opinion of the roles of the signal transducer Mps one binder 2 (MOB2) in the control of cell cycle progression and the DNA Damage Response (DDR). We recently found that endogenous MOB2 is required to prevent the accumulation of endogenous DNA damage in order to prevent the undesired, and possibly detrimental, activation of cell cycle checkpoints. In this regard, it is noteworthy that MOB2 has been linked biochemically to the regulation of the NDR1/2 (aka STK38/STK38L) protein kinases, which themselves have functions at different steps of the cell cycle. Therefore, we are speculating in this article about the possible connections of MOB2 with NDR1/2 kinases in cell cycle and DDR Signaling

The Strength of Absent Ties: Social Integration via Online Dating

We used to marry people to which we were somehow connected to: friends of friends, schoolmates, neighbours. Since we were more connected to people similar to us, we were likely to marry someone from our own race. However, online dating has changed this pattern: people who meet online tend to be complete strangers. Given that one-third of modern marriages start online, we investigate theoretically, using random graphs and matching theory, the effects of those previously absent ties in the diversity of modern societies. We find that when a society benefits from previously absent ties, social integration occurs rapidly, even if the number of partners met online is small. Our findings are consistent with the sharp increase in interracial marriages in the U.S. in the last two decades

Regulation of DNA damage responses and cell cycle progression by hMOB2.

Mps one binder proteins (MOBs) are conserved regulators of essential signalling pathways. Biochemically, human MOB2 (hMOB2) can inhibit NDR kinases by competing with hMOB1 for binding to NDRs. However, biological roles of hMOB2 have remained enigmatic. Here, we describe novel functions of hMOB2 in the DNA damage response (DDR) and cell cycle regulation. hMOB2 promotes DDR signalling, cell survival and cell cycle arrest after exogenously induced DNA damage. Under normal growth conditions in the absence of exogenously induced DNA damage hMOB2 plays a role in preventing the accumulation of endogenous DNA damage and a subsequent p53/p21-dependent G1/S cell cycle arrest. Unexpectedly, these molecular and cellular phenotypes are not observed upon NDR manipulations, indicating that hMOB2 performs these functions independent of NDR signalling. Thus, to gain mechanistic insight, we screened for novel binding partners of hMOB2, revealing that hMOB2 interacts with RAD50, facilitating the recruitment of the MRE11-RAD50-NBS1 (MRN) DNA damage sensor complex and activated ATM to DNA damaged chromatin. Taken together, we conclude that hMOB2 supports the DDR and cell cycle progression

Vaskomplexekkel katalizált oxidációs reakciók = Oxidation reactions catalyzed by iron complexes

Új kétmagvú vas(III)komplexeket állítottunk elő és azonosítottunk négyfogú N-donor ligandum, 1,4-di-(2'-piridil)aminoftalazin (PAP) felhasználásával. A [Fe2(mu-OMe)2(PAP)Cl4]*2MeOH komplex röntgendiffrakciós vizsgálata alapján megállapítottuk, hogy a 6-os koordinációjú, torzult oktaéderes geometriájú vas atomokat a PAP ligandum és a két metoxi csoport oxigénjei kapcsolják össze. Mindkét komplex katalizálja alkánok oxidációját hidrogén-peroxiddal. Primer és szekunder alkoholok oxidációját vizsgáltuk hidrogén-peroxiddal [(Fe2(ind)2(mu-O)Cl2] (indH = 1,3-bis(2'-pyridylimino)isoindoline) és [[Fe2(mu-OMe)2(PAP)Cl4] komplexek jelenlétében. Megállapítottuk, hogy acetonban mindkét komplex katalizálja alkoholok oxidációját a megfelelő karbonil vegyületekké. Új homoleptikus vas(II) komplexet állítottunk elő indH ligandum felhasználásával. A komplex inert dioxigénnel szemben, de katalizálja benzil-alkohol és hidrogén-peroxid reakcióját. Fe(ClO4)2 és indH reakciójával acetonitrilben [Fe(indH)(CH3CN)2](ClO4)2 komplexet szintetizáltunk. A komplex szerkezetét IR, UV-Vis, Mössbauer spektroszkópia és röntgendiffrakció alapján meghatároztuk. A komplex jó katalizátornak bizonyult benzil alkohol oxidációjában. | New dinuclear iron(III) complexes with tetradentate N-donor ligand 1,4-di(2'-pyridyl)aminophthalazine (PAP) were prepared and characterized. Single crystal X-ray molecular structure of [Fe2(MU-OMe)2(PAP)Cl4]*2MeOH show, that the six-coordinate iron atoms are in distorted octahedral environment bridged by the oxygen atoms of two methoxy groups and the PAP ligand. Both complexes showed catalytic activity for alkane oxidation with hydrogen peroxide. Oxidation of primary and secondary alcohols has been studied in the presence of [Fe(ind)Cl]2O (indH = 1,3-bis(2'-pyridylimino)isoindoline) and [Fe2(OMe)2(PAP)Cl4] as catalysts using hydrogen peroxide as primary oxidant. The complexes were found to be suitable catalysts for the oxidation of alcohols to the corresponding carbonyl compounds in acetone. New homoleptic iron(II) complex was prepared with indH as ligand. The complex is inert to dioxgen, but catalyzes the reaction of benzyl alcohol and hydrogen peroxide. Reaction of indH and Fe(ClO4)2 in acetonitrile resulted in the formation of [Fe(indH)(CH3CN)(H2O)2](ClO4)2. The composition and molecular structure of the complex was fully determined by IR, UV-Vis, Mössbauer and X-ray crystal analysis. The complex was found to be suitable catalyst for the oxidation of benzyl alcohols

Nemhem-vastartalmú modellek előállítása és gyakorlati alkalmazásai = Nonheme Iron-containing Enzyme Models and Their Possible Applications

A jelen kutatási pályázat olyan nemhem-vastartalmú metalloenzimek (Oldható metán monooxigenáz, 1-amino-ciklopropán-1-karbonsav oxidáz, flavonol 2,4-dioxigenáz, pirokatechin dioxigenáz, szuperoxid diszmutáz) szintetikus modellezésére irányult, amelyek dioxigént használnak fel. A szerkezeti modellek előállításához - az irodalomban fellelhető ligandumok (pl. Salen) mellett - új háromfogú izoindolin-típusú ligandumokat állítottunk elő, majd komplexképződési reakcióik (Fe, Mn, Cu, Co, Ni) tanulmányozása után bioutánzó sztöchiometrikus és katalitikus oxidációs reakciókat dolgoztunk ki. A reakciókinetikai mérések és a reaktív intermedierek azonosítása alapján javaslatot tettünk a reakciók mechanizmusára. | The aim of this project was to work out structural- and functional models for nonheme iron-containing metalloenzymes which utilize dioxygen (Soluble methane monooxygenase, 1-aminocyclopropane-1-carboxylic acid oxidase, catechol dioxygenase, superoxide dismutase etc.) . The research project comprised the synthesis and characterization of new tridentate isoindoline-type ligands and their iron, copper, manganese, cobalt and nickel complexes, studies of their oxidation reactions (selectivity, intermediates, mechanism etc.), and testing them as suitable catalysts in various biomimetic reactions

NDR Kinases Are Essential for Somitogenesis and Cardiac Looping during Mouse Embryonic Development

Studies of mammalian tissue culture cells indicate that the conserved and distinct NDR isoforms, NDR1 and NDR2, play essential cell biological roles. However, mice lacking either Ndr1 or Ndr2 alone develop normally. Here, we studied the physiological consequences of inactivating both NDR1 and NDR2 in mice, showing that the lack of both Ndr1/Ndr2 (called Ndr1/2-double null mutants) causes embryonic lethality. In support of compensatory roles for NDR1 and NDR2, total protein and activating phosphorylation levels of the remaining NDR isoform were elevated in mice lacking either Ndr1 or Ndr2. Mice retaining one single wild-type Ndr allele were viable and fertile. Ndr1/2-double null embryos displayed multiple phenotypes causing a developmental delay from embryonic day E8.5 onwards. While NDR kinases are not required for notochord formation, the somites of Ndr1/2-double null embryos were smaller, irregularly shaped and unevenly spaced along the anterior-posterior axis. Genes implicated in somitogenesis were down-regulated and the normally symmetric expression of Lunatic fringe, a component of the Notch pathway, showed a left-right bias in the last forming somite in 50% of all Ndr1/2-double null embryos. In addition, Ndr1/2-double null embryos developed a heart defect that manifests itself as pericardial edemas, obstructed heart tubes and arrest of cardiac looping. The resulting cardiac insufficiency is the likely cause of the lethality of Ndr1/2-double null embryos around E10. Taken together, we show that NDR kinases compensate for each other in vivo in mouse embryos, explaining why mice deficient for either Ndr1 or Ndr2 are viable. Ndr1/2-double null embryos show defects in somitogenesis and cardiac looping, which reveals their essential functions and shows that the NDR kinases are critically required during the early phase of organogenesis

Regulation of polarised growth in fungi

Polarised growth in fungi occurs through the delivery of secretory vesicles along tracks formed by cytoskeletal elements to specific sites on the cell surface where they dock with a multiprotein structure called the exocyst before fusing with the plasmamembrane. The budding yeast, Saccharomyces cerevisiae has provided a useful model to investigate the mechanisms involved and their control. Cortical markers, provided by bud site selection pathways during budding, the septin ring during cytokinesis or the stimulation of the pheromone response receptors during mating, act through upstream signalling pathways to localise Cdc24, the GEF for the rho family GTPase, Cdc42. Cdc42 in its GTP-bound activates a multiprotein protein complex called the polarisome which nucleates actin cables along which the secretory vesicles are transported to the cell surface. Hyphae can elongate at a rate orders of magnitude faster than the extension of a yeast bud, so understanding hyphal growth will require substantial modification of the yeast paradigm. The rapid rate of hyphal growth is driven by a structure called the Spitzenkörper, located just behind the growing tip and which is rich in secretory vesicles. It is thought that secretory vesicles are delivered to the apical region where they accumulate in the Spitzenkörper. The Spitzenkörper then acts as vesicle supply centre in which vesicles exit the Spitzenkörper in all directions, but because of its proximity, the tip receives a greater concentration of vesicles per unit area than subapical regions. There are no obvious equivalents to the bud site selection pathway to provide a spatial landmark for polarised growth in hyphae. However, an emerging model is the way that the site of polarised growth in the fission yeast, Schizosaccharomyces pombe, is marked by delivery of the kelch repeat protein, Tea1, along microtubules. The relationship of the Spitzenkörper to the polarisome and the mechanisms that promote its formation are key questions that form the focus of current research