Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage

Ataxia-telangiectasia mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are members of the phosphoinositide-3-kinase-related protein kinase (PIKK) family, and are rapidly activated in response to DNA damage. ATM and DNA-PKcs respond mainly to DNA double-strand breaks, whereas ATR is activated by single-stranded DNA and stalled DNA replication forks. In all cases, activation involves their recruitment to the sites of damage. Here we identify related, conserved carboxy-terminal motifs in human Nbs1, ATRIP and Ku80 proteins that are required for their interaction with ATM, ATR and DNA-PKcs, respectively. These motifs are essential not only for efficient recruitment of ATM, ATR and DNA-PKcs to sites of damage, but are also critical for ATM-, ATR- and DNA-PKcs-mediated signalling events that trigger cell cycle checkpoints and DNA repair. Our findings reveal that recruitment of these PIKKs to DNA lesions occurs by common mechanisms through an evolutionarily conserved motif, and provide direct evidence that PIKK recruitment is required for PIKK-dependent DNA-damage signalling.     

Lubrication by charged polymers

Long-ranged forces between surfaces in a liquid control effects from colloid stability to biolubrication, and can be modified either by steric factors due to flexible polymers, or by surface charge effects. In particular, neutral polymer 'brushes' may lead to a massive reduction in sliding friction between the surfaces to which they are attached, whereas hydrated ions can act as extremely efficient lubricants between sliding charged surfaces. Here we show that brushes of charged polymers (polyelectrolytes) attached to surfaces rubbing across an aqueous medium result in superior lubrication compared to other polymeric surfactants. Effective friction coefficients with polyelectrolyte brushes in water are lower than about 0.0006-0.001 even at low sliding velocities and at pressures of up to several atmospheres (typical of those in living systems). We attribute this to the exceptional resistance to mutual interpenetration displayed by the compressed, counterion-swollen brushes, together with the fluidity of the hydration layers surrounding the charged, rubbing polymer segments. Our findings may have implications for biolubrication effects, which are important in the design of lubricated surfaces in artificial implants, and in understanding frictional processes in biological systems.     

Actions d'un inhibiteur sélectif des acétylcholinestérases,le 3318 CT,sur la transmission neuromusculaire du chat

Summary 3318 CT [bis (piperidinomethylcoumaranyl-5) cetone dimethiodide], a specific inhibitor of acetylcholinesterase, antagonizes, in small dosages, the neuromuscular block induced by Flaxedil in the cat; in larger dosages, 3318 CT blocks the transmission: this paralysing action is not related to an accumulation of acetylcholine, as acetylcholine itself antagonizes it; decamethonium also restores, partially at least, the indirect contractions. Prostigmine and m-hydroxyphenyltrimethylammonium have no action. The neuromuscular block by 3318 CT thus appears as a competitive curarization in an animal with inhibited acetylcholinesterases. There was no indication that pseudo-cholinesterase can play a part in the neuromuscular transmission; whereas in the case of the vagal transmission such a possibility could not be ruled out.     

Monovalent fragments of rabbit anti-F9 immunoglobulins prevent mouse blastocyst formation]

Fab fragments of a Rabbit anti-F 9 serum do not disturb cleavage of Mouse embryos in culture but prevent blastocyst formation. This effect is reversible for a few hours. It is observed neither with Fab fragments directed against another surface antigen of blastomers nor with monovalent concanavalin A.     

The early differentiation of the perinotochordal connective tissue. A scanning and transmission electron microscopic study on chick embryos (author's transl)]

The early differentiation of the connective tissue was investigated in the perinotochordal zone of 2-3 day-old chick embryos. After characterizing the different tissue components by transmission electron microscopy, their arrangement and distribution were examined by SEM. The results are discussed with regard to the role of the extracellular material in embryonic tissue interactions.