Skip to main content
. 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 2. Sequence-Level View of ssDNA Formation via a Slipped-Strand Structure Leading to an AID-Induced Persistent Lesion.

Figure 2

Transcription or increased torsional stress in C-string sequences that display a B/A intermediate conformation can lead to transient strand slippage at direct repeats and generate ssDNA on each strand of DNA. While these transient slippage events may last only milliseconds or less before returning to a duplex conformation, AID can act to deaminate either C’s or meC’s within preferred single-stranded target sequences (WRC). The T’s generated from deamination of meC’s are removed more slowly than U’s and are thus more long-lived lesions. After the DNA resumes its duplex conformation, the resulting T:G mismatch is vulnerable to DNA repair enzymes, such as activated Artemis, that may convert these to DSBs. For chromosomal translocations that occur in human B cells, Artemis is activated during DSB repair at chromosome 14 (e.g., during V(D)J recombination or Ig class switch recombination). Failure to efficiently repair the chromosome 14 break coupled with simultaneous generation of DSB at a fragile zone can lead to events that favor chromosomal translocations.