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Updated: Aug 4, 2025

Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells
Published on: February 24, 2014
Self-inflicted DNA breaks in cell differentiation and cancer
Jan Benada1, Dalal Alsowaida2, Lynn A Megeney3
1Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen 2200 N, Denmark.
Abstract:
Self-inflicted DNA strand breaks are canonically linked with cell death pathways and the establishment of genetic diversity in immune and germline cells. Moreover, this form of DNA damage is an established source of genome instability in cancer development. However, recent studies indicate that nonlethal self-inflicted DNA strand breaks play an indispensable but underappreciated role in a variety of cell processes, including differentiation and cancer therapy responses. Mechanistically, these physiological DNA breaks originate from the activation of nucleases, which are best characterized for inducing DNA fragmentation in apoptotic cell death. In this review, we outline the emerging biology of one critical nuclease, caspase-activated DNase (CAD), and how directed activation or deployment of this enzyme can lead to divergent cell fate outcomes.
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