DNA damage response (DDR) pathways prevent genomic instability by inducing cell-cycle arrest, DNA repair or apoptosis following DNA damage, and are known to be inactivated in polyploid cells as well as in many cancers. Bretscher and Fox used the developing fly papillar cells — a naturally polyploid, cycling cell population — to explore how proliferating cells without an active DDR manage genomic instability. They revealed that, despite the accumulation of chromosome breaks, these cells continued to cycle and successfully segregated broken chromosomes into daughter nuclei. The Fanconi anaemia protein FANCD2 was then found to act independently of the core Fanconi anaemia pathway and other core DDR components to prevent missegregation of chromosome fragments into micronuclei and to sustain unperturbed papillar organogenesis. The mechanism by which FANCD2 ensures proper segregation of broken chromosomes, thereby allowing propagation of cells with unstable genomes, remains to be elucidated.
Bretscher, H. S. & Fox, D. T. Proliferation of double-strand break-resistant polyploid cells requires Drosophila FANCD2. Dev. Cell 37, 444–457 (2016)
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Strzyz, P. Cell thriving despite DNA damage. Nat Rev Mol Cell Biol 17, 396 (2016). https://doi.org/10.1038/nrm.2016.86