RNA Polymerase Collision versus DNA Structural Distortion: Twists and Turns Can Cause Break Failure

• Published in: Molecular cell Vol. 62; no. 3; pp. 327 - 334
• Main Authors: Pannunzio, Nicholas R., Lieber, Michael R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.05.2016
• Subjects: Animals; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Chromosomal Instability; DNA; DNA - chemistry; DNA - metabolism; DNA Damage; DNA, Bacterial - chemistry; DNA, Bacterial - metabolism; DNA, Fungal - chemistry; DNA, Fungal - metabolism; DNA-directed RNA polymerase; DNA-Directed RNA Polymerases - metabolism; Humans; mice; Models, Genetic; molecular biology; Neoplasms - enzymology; Neoplasms - genetics; Neoplasms - pathology; Nucleic Acid Conformation; RNA; transcription (genetics); Transcription, Genetic; turbulent flow
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2016.03.034

The twisting of DNA due to the movement of RNA polymerases is the basis of numerous classic experiments in molecular biology. Recent mouse genetic models indicate that chromosomal breakage is common at sites of transcriptional turbulence. Two key studies on this point mapped breakpoints to sites of either convergent or divergent transcription but arrived at different conclusions as to which is more detrimental and why. The issue hinges on whether DNA strand separation is the basis for the chromosomal instability or collision of RNA polymerases. In this Perspective, Pannunzio and Lieber discuss recent findings linking topological tension generated from transcription to genome rearrangements, framing the work in the historical context of research spanning the previous four decades.