Journal Club – April 2020

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.

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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

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