Abstract
The interplay of transcription, topological tension, and chromosome breakage is a subject of intense interest, but, with so many facets to the problem, it is difficult to test. Here, we vary the orientation of promoters relative to one another in a yeast system that permits sensitive detection of chromosome breaks. Interestingly, convergent transcription that would direct RNA polymerases into one another does not increase chromosome breakage. In contrast, divergent transcription that would create underwound and potentially single-stranded DNA does cause a marked increase in chromosome breakage. Furthermore, we examine the role that topoisomerases are playing in preventing genome instability at these promoters and find that Top2 is required to prevent instability at converging promoters.
Highlights
The events surrounding collision of RNA polymerases during transcription are complex and of universal relevance for all living organisms (Garcıa-Rubio and Aguilera, 2012; Hobson et al, 2012; Liu and Alberts, 1995; Prescott and Proudfoot, 2002)
We chose to construct a version of a gross chromosomal rearrangement (GCR) assay in S. cerevisiae (Chen and Kolodner, 1999)
Work from other labs has found that the vast majority of all events resulting in resistance to both 5-fluoroorotic acid (5-FOA) and canavanine are due to loss of genetic material from the end of the chromosome (Chen and Kolodner, 1999; Yadav et al, 2014)
Summary
Pannunzio and Lieber demonstrate that, in wild-type cells, divergent, but not convergent, transcription increases genome instability measured by gross chromosomal rearrangements. The function of topoisomerase II is critical for preventing instability at convergent promoters.
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