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Replication termination in Escherichia coli


Project Description

DNA replication is a crucial process for all forms of life. Organisms need to copy all their genetic information before they can grow or reproduce through cell division. To prevent corruption of the information in DNA, this duplication process must be accurate and fully-completed before a cell divides. Replication occurs in three stages: initiation, elongation and termination. Replication initiation occurs at sites known as origins of replication. Most bacteria have circular chromosomes and a single bi-directional replication origin called oriC. The replication machinery (replisome) replicates DNA via replication forks that proceed in both directions during elongation. These forks meet during termination, a phase we know little about. However, fork fusion has recently been identified as a surprising cause of genomic instability. In E. coli replication fork fusions are normally confined to the termination area by semi-permissive Tus-ter complexes. These complexes act as a one-way block to replication. We will use the simplified E. coli system to study a process that occurs in all life.

This project will define the molecular mechanics of replication fork fusion events and the molecular reasons for aberrant fork fusions. We have recently developed an in vitro system to study replication fork fusion. Active E. coli replisomes can be assembled on oriC plasmids and forks then collided with Tus-ter complexes. In this project you will use this system and other biochemical methods to discover more about the mechanics of converging replication forks during termination. This project will help us understand how the hundreds of fork fusions in eukaryotic cells are achieved and how their processing contributes to maintaining genomic stability. Insights into the factors that maintain genomic integrity will help our understanding of cancer, ageing and many hereditary diseases.

Funding Notes

The studentship is fully funded for three years by the Department of Biology and covers: (i) a tax-free annual stipend at the standard Research Council rate (£15,000 estimated for 2020 entry), (ii) research costs, and (iii) tuition fees at the UK/EU rate. The successful candidate will be required to contribute to departmental teaching by undertaking 30 hours/year demonstrating for Biology practicals.

References

Entry requirements: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, in a are invited to apply. We welcome applications from students with backgrounds in any relevant biosciences subject that provides the necessary skills, knowledge and experience the research project.

Start date: October 2020

How good is research at University of York in Biological Sciences?

FTE Category A staff submitted: 44.37

Research output data provided by the Research Excellence Framework (REF)

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