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Molecular mechanisms of break-induced replication

  • Full or part time
    Dr Svetlana Makovets
  • Application Deadline
    Saturday, August 31, 2019
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Maintenance of genome stability is vital for the survival and propagation of all forms of life. DNA replication threatens genome stability as replication forks often stall, collapse and break. Broken replication forks generate double-strand DNA breaks with a single end to repair. Such forks can be repaired by break-induced replication (BIR) – a homology-dependent mechanism which shares some similarity with homologous recombination. The aim of this project is to understand the dynamics of DNA synthesis during BIR and what role different proteins, such as DNA helicases, polymerases and nucleases play in this process.

We are also interested in understanding how BIR leads to telomere length changes. We have previously shown that cells with constitutively active BIR have longer telomeres. The connection between BIR and telomeres is relevant to cancer as the subset of telomerase-negative cancers maintain their telomeres via BIR. BIR might also be relevant to carcinogenesis at its early stages, when critically short telomeres might be subjected to this mechanism. Investigating these connections will shed light on our understanding of the interplay between DNA repair mechanisms and telomere maintenance in normal cells, cancer and ageing.

Our lab mainly works on budding yeast S.cerevisiae but we are currently expanding into mammalian systems. We use basic molecular biology techniques (clonings, Southern, northern, and western blotting, gene knockouts, PCRs and qPCRs, etc), classical genetics, as well as chromatin immunoprecipitation, live cell imaging, 2-dimentional gel electrophoresis, genomics, proteomics and other methods. We are looking for enthusiastic recent graduates with a Bachelor’s or Master’s degree in Molecular Biology, Genetics, Biochemistry or a relevant discipline, with a strong interest in genome stability and/or chromosome biology. The successful applicant will join a lab of two postdoctoral fellows and three PhD students and will be provided with thorough training and development in experimental research and career in science.

Before applying please carefully read the information below. To apply email your CV, full transcripts from your Bachelor’s and Master’s (if available) studies and a short cover letter to Please use the same email address if you have any further enquiries.

Funding Notes

This project will be funded from an MRC grant and the successful applicant will be hired as a full time Research Assistant who will be enrolled into the University of Edinburgh PhD program as a part-time PhD student. This financial arrangement will not affect in any way the students’ progress towards a successful PhD but because of the employment constrains only EU citizens can apply (any EU country applicant will be given an equal opportunity). The start date is flexible but is expected to be in autumn 2019.

References

Anand RP1, Lovett ST, Haber JE. (2013) Break-induced DNA replication. Cold Spring Harb Perspect Biol. 5(12):a010397. doi: 10.1101/cshperspect.a010397.
Vasianovich Y., Altmannova V., Kotenko O., Newton M., Krejci L., and Makovets S. (2017) Unloading of homologous recombination factors is required for restoring double-stranded DNA at damage repair loci. EMBO J. 36:213-231.

Vasianovich Y., Harrington L.A., and Makovets S. (2014) Break-induced replication requires DNA damage-induced phosphorylation of Pif1 and leads to telomere lengthening. PLOS Genetics 10(10):e1004679.

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

FTE Category A staff submitted: 109.70

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

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