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
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