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. Author manuscript; available in PMC: 2019 Jul 1.
Published in final edited form as: Trends Biochem Sci. 2018 May 4;43(7):490–498. doi: 10.1016/j.tibs.2018.04.004

Figure 3, Key Figure. Model of DSB Formation at Human Fragile Zones.

Figure 3, Key Figure

Fragile zones are prone to forming transient, non-B DNA structures based on biochemical [3, 4], enzymatic [2, 5, 25, 33], and genetic [5] data. Formation of ssDNA in the non-B state is enhanced by processes that separate the DNA strands (i.e., transcription) and increased torsional stress. The non-B structures (such as the slipped-strand structure depicted here) are short-lived, but, while formed, the ssDNA is vulnerable to damage. AID can attack ssDNA in human B cells and reactive oxygen species (ROS) can more easily oxidize DNA not protected within a DNA duplex. Oxidized bases generated by ROS and T:G mismatches generated by AID deamination of 5-methylcytosine represent long-lived, persistent lesions (relative to the efficient processing of uracil by uracil glycosylase) that, upon collapse of the non-B structure back to duplex DNA, create distortions recognized by activated Artemis nuclease and are cleaved. When the persistent lesions are adjacent on opposite strands of the DNA duplex, this process can result in a DSB.