The C. elegans SET-2/SET1 histone H3 Lys4 (H3K4) methyltransferase preserves genome stability in the germline.

Maintaining the integrity of genetic information across generations is essential for both cell survival and reproduction, and requires the timely repair of DNA damage. Histone-modifying enzymes play a central role in the DNA repair process through the deposition and removal of post-translational modifications on the histone tails. Specific histone modification act in the DNA repair process through the recruitment of proteins and complexes with specific enzymatic activities, or by altering the chromatin state at the site of DNA lesions. The conserved SET1/MLL family of histone methyltransferases (HMT) catalyzes methylation of histone H3 on Lysine 4 (H3K4), a histone modification universally associated with actively transcribed genes. Studies have focused on the role of SET1/MLL proteins in epigenetic regulation of gene expression. Much less is known on their role in the DNA repair process in a developmental context. Here we show that SET-2, the Caenorhabditis elegans orthologue of SET1, is required to preserve germline genome integrity over subsequent generations. Animals lacking the SET-2 catalytic subunit show a transgenerational increase in sensitivity to DNA damage-inducing agents that is accompanied by a defect in double-strand break (DSB) repair and chromosome fragmentation. These defects are not due to a failure to activate the DNA damage response (DDR) that allows detection, signaling and repair of DNA lesions, because cell cycle arrest and apoptosis, key components of this pathway, are efficiently induced in set-2 mutant animal. Rather, our results suggest that SET-2 plays a role in the transgenerational maintenance of genome stability by acting in DNA repair downstream of DDR signaling.

Mobility of cesium through the Callovo-Oxfordian claystones under partially saturated conditions.

The diffusion of cesium was studied in an unsaturated core of Callovo-Oxfordian claystone, which is a potential host rock for retrievable disposal of high-level radioactive wastes. In-diffusion laboratory experiments were performed on rock samples with water saturation degrees ranging from 81% to 100%. The analysis of both cesium concentration monitoring in the source reservoir and post-mortem cesium rock concentration profile of the samples was carried out using a chemical-transport code where the sorption of cesium was described by a multisite ion-exchange model. The results showed that cesium exhibited a clear trend related to the saturation degree of the sample. The more dehydrated the rock sample, the slower the decrease of cesium concentration, and the thinner the penetration depth of cesium was. The effective diffusion coefficient (De) for cesium decreased from 18.5 × 10(-11) m(2) s(-1) at full-saturation to 0.3 × 10(-11) m(2) s(-1) for the more dehydrated sample. This decrease is almost 1 order of magnitude higher than that for tritiated water (HTO), although a similar behavior could have been expected, since cesium is known to diffuse in the same parts of the pore space as HTO in fully saturated claystones.

Effect of temperature on the containment properties of argillaceous rocks: The case study of Callovo-Oxfordian claystones.

Heat generated by high level radioactive wastes could alter the performance of a clay repository. It was intended to investigate the effect of such a thermal period on the diffusive properties of Callovo-Oxfordian claystones. Thus, through-diffusion experiments with HTO, Cl-36, Na-22 and Cs-137 were performed before, during and after stages of heating at 80°C that lasted for up to one year. A special attention was paid to limit the occurrence of any chemical disturbance. Therefore (i) the temperature was raised to 80°C, then progressively brought back to 21°C, thanks to three intermediate temperature stages, and (ii) specific synthetic solutions were used for each temperature, chemistry of which being close to the equilibrium state, especially with respect to the carbonate and sulphate minerals. It was found that experiments carried out at 80°C showed a clear increase of the effective diffusion coefficient values for the four tracers with respect to those obtained at 21°C (by a factor of 3 for HTO and Cl-36, 5 for Na-22 and 2 for Cs-137). On the other hand, the porosity and rock capacity values did not exhibit any significant discrepancy between 21°C and 80°C, indicating no observable damage of both the pore conducing network and the sorption properties of clay minerals. The Stokes-Einstein relationship, based on the temperature dependency of the viscosity of bulk water, could be used to describe the temperature dependence of the diffusion of HTO and Cl-36 but failed to describe the diffusive evolution of the two sorbing cations, Na-22 and Cs-137. Furthermore, experiments performed after the thermal period led to diffusive properties well matching those obtained before heating. All these results suggest that at the lab scale the heating of rock samples would not alter the claystone containment properties.