FindAPhD Weekly PhD Newsletter | JOIN NOW FindAPhD Weekly PhD Newsletter | JOIN NOW

Homologous recombination at human centromeres – friend or foe?


   Sir William Dunn School of Pathology

  Prof Fumiko Esashi  Friday, December 09, 2022  Competition Funded PhD Project (Students Worldwide)

About the Project

The centromere is a region of chromatin that serves as a platform for the kinetochore machinery assembly, hence is essential for accurate chromosome segregation during cell division. Human centromeres are characterised by highly repetitive alpha-satellite DNA sequence, encompassing several mega-bases. This property allows for the robustness of centromere function in chromosome segregation. However, centromeres are also difficult-to-replicate and experience substantial mechanical stress during chromosome segregation, poising centromeres as prime candidates for sites of DNA breakage. Indeed, chromosomal breakage and translocation at centromeres are often found in cancer cells.

Recent works from the Esashi group revealed that the central homologous recombination (HR) repair enzyme, the RAD51 recombinase, prevents centromere fragility in cells exposed to mild replication stress (1, 2, 3). However, the full picture of the mechanism by which RAD51 acts at centromeres is unclear. Further, while centromeres have been known to be highly recombinergic and rapidly evolving, it remains enigmatic whether HR at centromeres is truly advantageous (friend) or harmful (foe).  

This project tackles this fundamental question by exploiting innovative experimental approaches that enables the direct assessment of the level of DNA damage at centromeres in human cells. The study will use multidisciplinary approaches, such as biochemistry, genetics, advanced light microscopy and next- or third- generation sequencing. The project offers a unique training opportunity for student to interact with a powerful team of experts in the fields of DNA repair, recombination and replication and cell division.


Funding Notes

4 Year DPhil Prize Studentships cover full University fees, a tax free enhanced stipend of ~£20,168 pa, and up to £5,300 pa for research costs and travel. The competition is open to applicants from all countries. See View Website for full details and to apply.

References

1. Yata et al. (2012) PLK1 and CK2 act in concert to regulate RAD51 during DNA double strand break repair Mol Cell 45, 371-83.
2. Yata et al., (2014) BRCA2 coordinates the activities of cell-cycle kinases to promote genome stability Cell Reports 7,1547-1559
3. Wassing I.E. et al. (2021) The RAD51 recombinase protects mitotic chromatin in human cells Nat Commun. 12, 5380.

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


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

Click here to see the results for all UK universities
Search Suggestions
Search suggestions

Based on your current searches we recommend the following search filters.

PhD saved successfully
View saved PhDs