Nuclear conflict – resolving transcription-replication clashes

NIEDUSZYNSKI_E23DTP1

DNA replication and transcription are essential processes for all life on earth. However, a specific DNA sequence can only be engaged in either replication or transcription at any one time. As a result, conflicts frequently arise between transcription and replication processes, which have the potential to cause genome instability. Cells have efficient pathways to prevent transcription-replication conflicts. However, these pathways are not well understood. We have recently developed a novel genomic technology that can detect transcription-replication conflicts – this will allow us to discover pathways that the cell uses to protect the genome.

We offer a highly collaborative multi-disciplinary PhD between the Nieduszynski (DNA replication; technology development) and Haerty (DNA transcription; bioinformatics) groups. The main aim of the project is to determine the mechanisms employed by the cell to resolve the inevitable conflicts between DNA transcription and DNA replication.

The student will work in a rapidly developing field and gain a unique expertise in nanopore single molecule sequencing, technology development and computational biology – skills that are in high demand for modern biological research in both academia and industry. The project will be conducted at the Earlham Institute, a BBSRC-supported, world-leading research centre for bioinformatics and genome biology. The student will have access to training and career development opportunities at the Earlham Institute and on the Norwich Research Park as part of the Norwich Biosciences Doctoral Training Partnership.

References

Müller, C. A. et al. Capturing the dynamics of genome replication on individual ultra-long nanopore sequence reads. Nat Methods 16, 429–436 (2019).

Boemo, M. A. DNAscent v2: detecting replication forks in nanopore sequencing data with deep learning. BMC Genomics 22, 430 (2021).

Gómez-González, B. & Aguilera, A. Transcription-mediated replication hindrance: a major driver of genome instability. Gene Dev 33, 1008–1026 (2019).