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Modulation of transcription by DNA helicases

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

About This PhD Project

Project Description

DNA helicases are highly modular proteins that comprise ATP-dependent DNA motor domains coupled to “accessory” domains which often direct the enzyme to appropriate cellular targets (for review see [1]). We and others have recently discovered that several bacterial helicases harbour accessory domains that interact with RNA polymerase (for examples see [2] and [3]). In many cases however, the role of such interactions in modulating the activity of RNA polymerase is unclear. They might help to suppress the damaging effects of collisions between the replication and transcription machinery, which would otherwise lead to genomic instability and/or DNA repair [4].

In this project we will investigate the structural basis for helicase-RNA polymerase interactions, and will use biochemical techniques to study how the interaction affects the properties of both the helicase(s) and the RNA polymerase. Students will receive interdisciplinary training in biochemistry (protein/DNA purification and characterisation, DNA:protein interaction analysis, enzyme assays) and biophysics (bulk and single molecule kinetics, TIRF-based single molecule imaging, structural biology). The project will be co-supervised by Prof. Nigel Savery, also a member of the DNA:protein interactions unit in Bristol, and is part of a longstanding collaboration with Prof. Pete McGlynn at the University of York.


[1] Dillingham MS. Superfamily I helicases as modular components of DNA-processing machines. Biochem Soc Trans. 2011 Apr;39(2):413-23.

[2] Gwynn EJ et al. The conserved C-terminus of the PcrA/UvrD helicase interacts directly with RNA polymerase. PLoS One. 2013 Oct 16;8(10):e78141.

[3] Wiedermannová J et al. Characterization of HelD, an interacting partner of RNA polymerase from Bacillus subtilis. Nucleic Acids Res. 2014 Apr;42(8):5151-63.

[4] McGlynn P et al. The conflict between DNA replication and transcription. Mol Microbiol. 2012 Jul;85(1):12-20.

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