Abstract:

Chromosome replication in eukaryotes is carried out by a macromolecular machine termed the replisome. My research has been focused on understanding how the replisome is able to accurately and efficiently replicate the eukaryotic genome. In order to do so, I have assembled fully functional replisomes in vitro and then used a combination of structural and biochemical methods to understand the mechanistic details of their function. This approach has been successful in revealing the complex architecture of the core human replisome, determining how the Pol α-primase complex is recruited to the replisome to prime DNA synthesis, and how replication termination is regulated in eukaryotes. More recently, these approaches have expanded our understanding of how the accessory replisome component Mrc1 is coordinated at the replication fork, suggesting a mechanism for how it is able to stimulate DNA replication.

Bio:

Morgan did his doctoral studies at the Francis Crick Institute in London, in the group of Neil McDonald. During his PhD, Morgan trained as a structural biologist and used cryo-electron microscopy to study the role of the XPF-ERCC1 nuclease during DNA repair.

Morgan then moved to the MRC LMB in Cambridge and joined the group of Joe Yeeles, who is a world leader in reconstituting human DNA replication forks in vitro with purified proteins. Morgan determined the first structure of the core human replisome which provided a platform to investigate larger and more elaborate replisome assemblies. Building upon this work, Morgan provided important insights into how DNA synthesis is primed, as well as defining an important mechanism that prevents premature ubiquitylation and disassembly of the replication machinery.

Publications

How Pol a-primase is targeted to replisomes to prime eukaryotic DNA replication.

Jones ML, Aria V, Baris Y, Yeeles JTP. Mol Cell. 2023 Aug 17;83(16):2911-2924.e16. doi: 10.1016/j.molcel.2023.06.035. Epub 2023 Jul 27.

Structure of a human replisome shows the organisation and interactions of a DNA replication machine. Jones ML, Baris Y, Taylor MRG, Yeeles JTP. EMBO J. 2021 Dec 1;40(23):e108819. doi: 10.15252/embj.2021108819. Epub 2021 Oct 25.

A conserved mechanism for regulating replisome disassembly in eukaryotes. Jenkyn-Bedford M, Jones ML, Baris Y, Labib KPM, Cannone G, Yeeles JTP, Deegan TD. Nature. 2021 Dec;600(7890):743-747. doi: 10.1038/s41586-021-04145-3. Epub 2021 Oct 26.

Cryo-EM structures of the XPF-ERCC1 endonuclease reveal how DNA-junction engagement disrupts an auto-inhibited conformation. Jones M, Beuron F, Borg A, Nans A, Earl CP, Briggs DC, Snijders AP, Bowles M, Morris EP, Linch M, McDonald NQ. Nat Commun. 2020 Feb 28;11(1):1120. doi: 10.1038/s41467-020-14856-2.

Optimised oligonucleotide substrates to assay XPF-ERCC1 nuclease activity for the discovery of DNA repair inhibitors. Adam M Thomas , Sanja Brolih , Joanna F McGouran , Afaf H El-Sagheer , Denis Ptchelkine , Morgan Jones , Neil Q McDonald , Peter J McHugh, Tom Brown. Chem Commun (Camb). 2019 Sep 26;55(78):11671-11674. doi: 10.1039/c9cc05476f.