Chromosome Bridges, DNA Webs, and Tubulin Citrullination
Mechanisms Generating Cancer Genome Complexity From A Single Cell Division Error
Umbreit, Zhang et al. | Pellman Lab | Science
Theories on the origin of cancer have historically centered on the gradual accumulation of deleterious genomic alterations over time. In recent years, however, researchers have discovered that a single cellular catastrophe can induce massive genomic remodeling capable of driving human cancers. One such catastrophic event is the chromosome breakage-fusion-bridge (BFB) cycle, which results in the formation of a chromosome bridge during anaphase. In this study, Umbreit et al. discover that actomyosin-dependent bridge stretching and subsequent breakage unleash a “storm of mutagenesis” encompassing chromothripsis, aberrant DNA replication, and DNA damage. The convergence of these major mutagenizing mechanisms explains how a single cell division error can trigger the rapid accrual of complex karyotypes found in cancer.
Did you see our Special Issue last month on the interplay between coronaviruses and the cytoskeleton?
Read it here.
Image Credit: Maria Voigt/RCSB PDB
Journal Club Picks (find us in the methods section)
- It only takes 7 yeast proteins to reconstitute actin cables in vitro.
Pollard et al. | Goode Lab | Molecular Biology of the Cell
- A point mutation uncouples the mechanochemical cycle in mammalian tubulin.
Ye et al. | Rice Lab | Protein Science
- New structures of tubulin bound to phosphate analogues challenge existing GTP-cap models.
Estévez-Gallego et al. | Oliva Lab | eLife
- Cold temperatures lock tubulin in an assembly-incompetent conformation.
Liand and Moore | Moore Lab | Molecular Biology of the Cell
- A yeast glucokinase with an actin fold polymerizes upon sugar addition.
Stoddard et al. | Murray and Garner Labs | Science
- Tubulin citrullination – the conversion of arginine to citrulline – impacts microtubule dynamics.
Li et al. | Cherrington Lab | International Journal of Molecular Sciences
- Tubulin detyrosination patterns cue the correction of mitotic errors.
Ferreira et al. | Maiato Lab | Journal of Cell Biology
- Rapid actin disassembly enables white blood cells to secrete pathogen-trapping DNA webs.
Thiam et al. | Waterman Lab | Proceedings of the National Academy of Sciences
- An inhibitor of doublecortin like kinase 1 demonstrates activity in patient-derived organoids.
Ferguson et al. | Gray Lab | Nature Chemical Biology
Our opinions are our own and do not represent the views or endorsement of the authors cited.