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Telomere integrity: How do Replication Factor C-like complexes maintain telomere length?

Project Description

Telomeres, the ends of eukaryotic chromosomes, play an essential role in protecting linear DNA from degradation. Derailed telomere regulation causes genome instability and has been implicated in increased rates of cellular senescence and many diseases, including cancer. The length of telomeres is maintained by a coordinated action of telomerase and chromatin proteins acting at telomeres. The elongation of telomeres is coupled with DNA replication and occurs during late S phase. However, it is still unknown how the DNA replication machinery contributes to telomere maintenance.

The Elg1 and Ctf18 Replication Factor C-like complexes (Elg1-RLC and Ctf18-RLC) are important for telomere length maintenance. Loss of Elg1 causes telomere elongation, while loss of Ctf18 in contrast causes telomere shortening, in the model organism budding yeast Saccharomyces cerevisiae. Both Elg1-RLC and Ctf18-RLC act during DNA replication and control PCNA, a central DNA replication regulator acting as a sliding platform recruiting many replication proteins. However, how Elg1-RLC and Ctf18-RLC maintain the length of telomeres remains to be elucidated. In this project, the student will investigate how Elg1-RLC and Ctf18-RLC maintain telomere integrity using genetics and proteomics. For example, the student will investigate abnormality in composition of telomeric proteins at telomeres in cells lacking Elg1 or Ctf18, and how PCNA is related to the abnormality. This project will reveal how DNA replication is coupled with telomere maintenance event, and will give us an insight into how derailed telomere maintenance is associated with tumorigenesis, as loss of human Elg1-RLC and over-production of human Ctf18-RLC are linked to tumorigenesis.

This project is advertised in relation to the research areas of MEDICAL SCIENCES. Formal applications can be completed online: You should apply for Degree of Doctor of Philosophy in Medical Sciences, to ensure that your application is passed to the correct person for processing.

NOTE CLEARLY THE NAME OF THE SUPERVISOR AND EXACT PROJECT TITLE ON THE APPLICATION FORM. Applicants are limited to applying for a maximum of 3 applications for funded projects. Any further applications received will be automatically withdrawn.

Funding Notes

This project is funded by a University of Aberdeen Elphinstone Scholarship. An Elphinstone Scholarship covers the cost of tuition fees only, whether home, EU or overseas.

For details of fees: View Website

Candidates should have (or expect to achieve) a minimum of a First Class Honours degree in a relevant subject. Applicants with a minimum of a 2:1 Honours degree may be considered provided they have a Distinction at Masters level.

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