Building the Future Therapies for Down Syndrome: The Third International Conference of the T21 Research Society

Research focused on Down syndrome has increased in the last several years to advance understanding of the consequences of trisomy 21 (T21) on molecular and cellular processes and, ultimately, on individuals with Down syndrome. The Trisomy 21 Research Society (T21RS) is the premier scientific organization for researchers and clinicians studying Down syndrome. The Third International Conference of T21RS, held June 6–9, 2019, in Barcelona, Spain, brought together 429 scientists, families, and industry representatives to share the latest discoveries on underlying cellular and molecular mechanisms of T21, define cognitive and behavioral challenges and better understand comorbidities associated with Down syndrome, including Alzheimer’s disease and leukemia. Presentation of cutting-edge results in neuroscience, neurology, model systems, psychology, cancer, biomarkers and molecular and phar­ma­cological therapeutic approaches demonstrate the compelling interest and continuing advancement in all aspects of understanding and ameliorating conditions associated with T21

Reactivity of DNA and cis-Diamminedichloroplatinumul(II) in the Presence of Intercalating Agents

International audienceThe antitumor drug cis-diamminedichloroplatinum(II) (cis-DDP) is assumed to exhibit its toxicity by reacting with cellular DNA. Lesions produced in DNA have been characterized as bifunctional adducts including mainly intrastrand and interstrand cross-links. It is not yet known which lesion(s) is(are) responsible for selective destruction of tumor cells1–3. Drugs known to bind to DNA such as doxorubicin or bleomycin are commonly used therapeutically in combination with cis-DDP4. In vitro several studies have shown the mutual influence of cis-DDP and drugs binding to DNA5–11. One purpose of our work is to better understand how the binding of cis-DDP can be altered by the presence of other drugs interacting also with DNA. In this paper, we first show that RNA polymerases are a convenient tool to detect the adducts formed in the in vitro reaction between DNA and cis-DDP. In particular, we find that the interstrand adducts are formed at the d(GC) sites. Then, we show that a new kind of adduct, a DNA-monocoordinated complex, is formed when the reaction of platination is done in the presence of some intercalating agents. In this reaction, the DNA double helix first favors the formation of the new adduct and then favors the release of a platinum derivative. These results are discussed in relation with a catalytic activity of the DNA double helix