Physiological Chemistry

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The team led by Nicolai Siegel has uncovered a mechanism that enables the parasite that causes sleeping sickness in humans to escape the attention of the immune system. Nicolai's group, in collaboration with colleagues at the University of Dundee, have now elucidated an important step in the mechanism that controls surface-antigen variation. They have identified a three-dimensional structure in the nucleus of T. brucei that serves as a separate compartment, in which the mRNA molecules that encode the cell’s single surface protein variant are modified. As a result, they avoid rapid destruction, and therefore survive long enough to produce the protein in the required amount. The finding may also be relevant to other infectious diseases. more

We identified an enzyme that is essential for DNA repair. In its absence cancer cells accumulate DNA damage. We used PARP inhibitors (PARPi) to treat BRCA-deficient tumors and reveal how PARPi trap PARP2 on damaged chromatin. We show that the oncogenic helicase Alc1 is required for its release and Alc1 potentiates PARPi-induced cancer killing through PARP2 trapping. more