Do transcription factories and TOP2B provide a recipe for chromosome translocations in therapy-related leukemia?

Abstract

Comment on: Cowell IG, et al. Proc Natl Acad Sci USA 2012; 109:8989-94.

Figure 1. Organization of transcription units into transcription factories and transcription factory model for t-AL-associated chromosome translocations. The focal nature of transcription could facilitate chromosome translocation. Active genes located on different chromosomes (red and blue) can share common transcription factories. Ongoing transcription in a shared transcription factory can maintain two heterologous chromosome segments in juxtaposition for the length of the transcription cycle, and it is hypothesized that this facilitates translocation when DNA breaks are induced. In the case of t-AL, translocations breaks are introduced by the action of TOP2 poisons on TOP2B during transcription. Diagram adapted from Cook, et al.