Dr Morgan Jones
Our goal is to understand how DNA replication is coordinated with the many other processes operating on the genome, and how this coordination preserves genome integrity
Dr Morgan Jones
DNA Replication in a Dynamic Genome
All cells must faithfully duplicate their genome before they divide. This essential process is carried out by the replisome, a macromolecular machine that unwinds and copies DNA. Far from operating on an isolated DNA template, the replisome must function within the densely populated environment of the chromosome. The same DNA molecule being replicated may be simultaneously transcribed, repaired, packaged into chromatin and accessed by numerous protein complexes.
Our research seeks to understand how DNA replication is coordinated within this complex molecular landscape. To achieve this, we reconstitute human DNA replication from purified components, enabling us to dissect, under precisely controlled conditions, how the replisome responds to the diverse obstacles it encounters during genome duplication.
A major focus of our work is understanding collisions between the replisome and the transcription machinery. We combine biochemical reconstitution with cryo-electron microscopy, cross-linking mass spectrometry and single-molecule approaches to capture and characterise these encounters at molecular resolution. By integrating these complementary techniques, we aim to understand how transcription-replication conflicts threaten genome integrity, and explore the pathways cells use to prevent, tolerate and resolve them.
