Completion of DNA replication needs to be ensured even when challenged with fork progression problems or DNA damage. PCNA and its modifications constitute a molecular switch to control distinct repair pathways. In yeast, SUMOylated PCNA (S-PCNA) recruits Srs2 to sites of replication where Srs2 can disrupt Rad51 filaments and prevent homologous recombination (HR). We report here an unexpected additional mechanism by which S-PCNA and Srs2 block the synthesis-dependent extension of a recombination intermediate, thus limiting its potentially hazardous resolution in association with a cross-over. This new Srs2 activity requires the SUMO interaction motif at its C-terminus, but neither its translocase activity nor its interaction with Rad51. Srs2 binding to S-PCNA dissociates Polδ and Polη from the repair synthesis machinery, thus revealing a novel regulatory mechanism controlling spontaneous genome rearrangements. Our results suggest that cycling cells use the Siz1-dependent SUMOylation of PCNA to limit the extension of repair synthesis during template switch or HR and attenuate reciprocal DNA strand exchanges to maintain genome stability.

Toxoplasma gondii is a zoonotic protozoan with a worldwide occurrence, but the determinants of the current pattern in the geographical distribution of T . gondii lineages and strains remain poorly understood. To test the influence of human trade on T . gondii populations, we conducted a population genetic study of 72 T . gondii animal isolates from Senegal, a West African country in which the ongoing inland progress of invasive murine hosts (introduced in port cities of Senegal since the 16 th century by European sailors) is well described. Isolates were mainly collected on free-range poultry, which are considered as relevant bioindicators of T . gondii strain diversity in the domestic environment. Sampling was conducted in two port cities of Senegal (Dakar and Saint-Louis) and in one inland region (Kedougou). Population genetic analyses using 15 microsatellite markers revealed different patterns between port cities where lineages non-virulent for mice (type II, type III, and Africa 4) were predominant, and Kedougou where the mouse-virulent Africa 1 lineage was the most common. By considering the current spatial pattern in the inland progress of invasive rodents in Senegal, our results suggest that the invasive house mouse Mus musculus domesticus counter-selects the Africa 1 lineage in the invaded areas. The comparison of the microsatellite alleles of type II strains from Senegal to type II strains from other areas in Africa and Western Europe, using discriminant analysis of principal components and Network analysis, point to a mainly Western European origin of the type II lineage in Senegal. Collectively, these findings suggest that human-mediated intercontinental migrations of murine hosts are important vectors of T . gondii strains. Differential susceptibility of endemic and introduced murine hosts to various T . gondii strains probably determines the persistence of these strains in the environment, and therefore their availability for human and animal infection.

Toxoplasmosis, one of the most prevalent parasitic infections in humans and animals, is caused by the intracellular protozoan parasite Toxoplasma gondii. Small mammals play a key role as intermediate reservoir hosts in the maintenance of the T. gondii life cycle. In this study, we estimated the molecular prevalence and provide genetic diversity data for T. gondii in 632 small mammals sampled in four areas of Cotonou city, Benin. Both the brain and heart of each individual were screened through T. gondii-targeting qPCR, and positive samples were then genotyped using a set of 15 T. gondii-specific microsatellites. Prevalence data were statistically analyzed in order to assess the relative impact of individual host characteristics, spatial distribution, composition of small mammal community, and urban landscape features. An overall T. gondii molecular prevalence of 15.2% was found and seven genotypes, all belonging to the Africa 1 lineage, could be retrieved from the invasive black rat Rattus rattus and the native African giant shrew Crocidura olivieri. Statistical analyses did not suggest any significant influence of the environmental parameters used in this study. Rather, depending on the local context, T. gondii prevalence appeared to be associated either with black rat, shrew, or mouse abundance or with the trapping period. Overall, our results highlight the intricate relationships between biotic and abiotic factors involved in T. gondii epidemiology and suggest that R. rattus and C. olivieri are two competent reservoirs for the Africa 1 lineage, a widespread lineage in tropical Africa and the predominant lineage in Benin.