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Updated: Jun 15, 2025

Antibiotic Dereplication Using the Antibiotic Resistance Platform
Published on: October 17, 2019
ADARp150 counteracts whole genome duplication
Frank van Gemert1, Alexandra Drakaki1, Isabel Morales Lozano1
1Division of Tumor Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Abstract:
Impaired control of the G1/S checkpoint allows initiation of DNA replication under non-permissive conditions. Unscheduled S-phase entry is associated with DNA replication stress, demanding for other checkpoints or cellular pathways to maintain proliferation. Here, we uncovered a requirement for ADARp150 to sustain proliferation of G1/S-checkpoint-defective cells under growth-restricting conditions. Besides its well-established mRNA editing function in inversely oriented short interspersed nuclear elements (SINEs), we found ADARp150 to exert a critical function in mitosis. ADARp150 depletion resulted in tetraploidization, impeding cell proliferation in mitogen-deprived conditions. Mechanistically we show that ADAR1 depletion induced aberrant expression of Cyclin B3, which was causative for mitotic failure and whole-genome duplication. Finally, we find that also in vivo ADAR1-depletion-provoked tetraploidization hampers tumor outgrowth.
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