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Pappas, G.

Publications and source records attributed to Pappas, G..

2 recordsLinked to original sources

New insights on adaptation and population structure of cork oak using genotyping by sequencing

Species respond to global climatic changes in a local context. Understanding this process is paramount due to the pace of these changes. Tree species are particularly interesting to study in this regard due to their long generation times, sedentarism, and ecological and economic importance. Quercus suber L. is an evergreen forest tree species of the Fagaceae family with an essentially Western Mediterranean distribution. Despite frequent assessments of the species evolutionary history, large-scale genetic studies have mostly relied on plastidial markers, whereas nuclear markers have been used on studies with locally focused sampling strategies. The potential response of Q. suber to global climatic changes has also been studied, under ecological modelling. In this work, \"Genotyping by Sequencing\" (GBS) is used to derive 2,547 SNP markers to assess the species evolutionary history from a nuclear DNA perspective, gain insights on how local adaptation may be shaping the species genetic background, and to forecast how Q. suber may respond to global climatic changes from a genetic perspective. Results reveal an essentially unstructured species, where a balance between gene flow and local adaptation keeps the species gene pool somewhat homogeneous across its distribution, but at the same time allows variation clines for the individuals to cope with local conditions. \"Risk of Non-Adaptedness\" (RONA) analyses, suggest that for the considered variables and most sampled locations, the cork oak does not require large shifts in allele frequencies to survive the predicted climatic changes. However, more research is required to integrate these results with those of ecological modelling.

evolutionary biology

Mutational signatures reveal the role of RAD52 in p53-independent p21 driven genomic instability

BackgroundGenomic instability promotes evolution and heterogeneity of tumors. Unraveling its mechanistic basis is essential to design appropriate therapeutic strategies. In a recent study we reported an unexpected oncogenic property of p21WAF1/Cip1 showing that its chronic expression, in a p53-deficient environment, causes genomic instability by deregulating the replication licensing machinery.\n\nResultsExtending on this work we now demonstrate that p21WAF1/Cip1 can further fuel genomic instability by suppressing the repair capacity of low and high fidelity pathways that deal with nucleotide abnormalities. Consequently, fewer single nucleotide substitutions (SNSs) occur, while formation of highly deleterious DNA double-strand breaks (DSBs) is enhanced, crafting a characteristic mutational signature landscape. Guided by the mutational signatures formed, we found at the mechanistic level that the DSBs were repaired by Rad52-dependent Break-Induced Replication (BIR) and Single-Strand Annealing (SSA). Conversely, the error-free synthesis-dependent strand annealing (SDSA) repair route was deficient. Surprisingly, Rad52 was activated transcriptionally in an E2F1-dependent manner, rather than post-translationally as is common for DNA repair factor activation.\n\nConclusionsOur results signify the importance of mutational signatures as guides to disclose the \"repair history\" leading to genomic instability. In this vein, following this approach we unveiled how chronic p21WAF1/Cip1 expression rewires the repair process, identifying Rad52 as a source of genomic instability and a candidate therapeutic target.

cancer biology