Prospects & Overviews
Pausing for thought: Disrupting the early transcription elongation checkpoint leads to developmental defects and tumourigenesis
Article first published online: 10 APR 2013
© 2013 WILEY Periodicals, Inc.
Volume 35, Issue 6, pages 553–560, June 2013
How to Cite
Jennings, B. H. (2013), Pausing for thought: Disrupting the early transcription elongation checkpoint leads to developmental defects and tumourigenesis. Bioessays, 35: 553–560. doi: 10.1002/bies.201200179
- Issue published online: 15 MAY 2013
- Article first published online: 10 APR 2013
- Manuscript Accepted: 4 MAR 2013
- Manuscript Received: 20 DEC 2012
- Career Development Award from the UK Medical Research Council (MRC) and Project Grant from the Wellcome Trust
- promoter proximal pausing;
- transcription elongation
Factors affecting transcriptional elongation have been characterized extensively in in vitro, single cell (yeast) and cell culture systems; however, data from the context of multicellular organisms has been relatively scarce. While studies in homogeneous cell populations have been highly informative about the underlying molecular mechanisms and prevalence of polymerase pausing, they do not reveal the biological impact of perturbing this regulation in an animal. The core components regulating pausing are expressed in all animal cells and are recruited to the majority of genes, however, disrupting their function often results in discrete phenotypic effects. Mutations in genes encoding key regulators of transcriptional pausing have been recovered from several genetic screens for specific phenotypes or interactions with specific factors in mice, zebrafish and flies. Analysis of these mutations has revealed that control of transcriptional pausing is critical for a diverse range of biological pathways essential for animal development and survival.