In our lab, we investigate the mechanisms that drive changes in the genome during cell growth and dormancy. We are particularly interested in the trigger of these changes, how cells protect themselves against dangerous changes and, in what situations, they adapt to them for gain. By studying these processes, we hope to uncover new insights into the molecular basis of human diseases.
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RAD51 enrichment at sites of DNA breaks (A) and RAD51-mediated HR (B)
Direct detection of DNA breaks in repetitive regions of human genome
The stability and evolution of the genome are central to many living organisms for their continued growth, survival and reproduction. Commonly, a genome is referred to as the complete set of genetic information in an organism. However, the full decoding of the human genome revealed a plethora of seemingly non-functional repeat sequences, taking up more than half of the genomic DNA. It remains unclear to what extent such regions contribute to disease-causing genome instability or advantageous genome evolution.
Tackling this problem, we study triggers and regulation of an evolutionary highly conserved mechanism called homologous recombination (HR). HR can exchange genomic elements based upon ‘homologous’ (i.e. similar in position, structure, and evolutionary origin) DNA sequences. As such, it impacts genome stability either positively or negatively.
HR normally occurs during S and G2 phases of the cell cycle and, by using the replicated sister DNA as a repair template, can faithfully recover the missing genomic information. However, HR can also use a similar but non-allelic DNA as a repair template, and by doing so, exchange, amplify or delete repetitive regions of genomic DNA. Such non-allelic HR events could result in genome instability, but could conversely offer, in some situations, structural or functional robustness.
We aim to understand how HR is regulated in the context of the cell cycle and at regions of genomic DNA that are prone to break or recombine. We use and develop interdisciplinary approaches combining various state-of-the-art tools to investigate the impact of HR on genome stability. These include, but not limited to, genetics, molecular biology, microscopy imaging, biochemistry, bioinformatics and mathematical modelling.
2023
Centromeres as universal hotspots of DNA breakage, driving RAD51-mediated recombination during quiescence.
Saayman, X., Graham, E., Nathan, W.J., Nussenzweig, A. and Esashi, F.
Molecular Cell – 83: 523-538.e7.
2022
KAT2-mediated acetylation switches the mode of PALB2 chromatin association to safeguard genome integrity.
Fournier, M., Rodrigue, A., Milano, L., Bleuyard, J.Y., Couturier, A.M., Wall, J., Ellins, J., Hester, S., Smerdon, S.J., Tora, L., Masson, J.Y. and Esashi, F.
eLife – 11: e57736.
2021
The RAD51 recombinase protects mitotic chromatin in human cells.
Wassing, I.E., Graham, E., Saayman, X., Rampazzo, L., Ralf, C., Bassett, A. and Esashi, F.
Nature Communications – 12(1): 5380.
2020
Molecular flexibility of DNA as a key determinant of RAD51 recruitment.
Paoletti, F., El-Sagheer, A.H., Allard, J., Brown, T., Dushek, O. and Esashi, F.
EMBO J. – 39: e103002.
2017
MRG15-mediated tethering of PALB2 to unperturbed chromatin protects active genes from genotoxic stress.
Bleuyard, J.Y., Fournier, M., Nakato, R., Couturier, A.M., Katou, Y., Ralf, C., Hester, S.S., Dominguez, D., Rhodes, D., Humphrey, T.C., Shirahige, K. and Esashi, F.
Proc Natl Acad Sci U S A. – 114: 7671-7676.
2014
BRCA2 coordinates the activities of cell-cycle kinases to promote genome stability.
Yata, K., Bleuyard, J.Y., Nakato, R., Ralf, C., Katou, Y., Schwab, R.A., Niedzwiedz, W., Shirahige, K. and Esashi, F.
Cell Rep. – 7: 1547-1559.
2012
Plk1 and CK2 act in concert to regulate Rad51 during DNA double strand break repair.
Yata, K., Lloyd, J., Maslen, S., Bleuyard, J.Y., Skehel, M., Smerdon, S.J. and Esashi, F.
Molecular Cell – 45: 371-83.
2012
ChAM, a novel motif that mediates PALB2 intrinsic chromatin binding and facilitates DNA repair.
Bleuyard, J.Y., Buisson, R., Masson, J.Y. and Esashi, F.
EMBO Rep. – 13: 135-41.
Fumiko Esashi Receives BBSRC Grant for Centromere Evolution Research
November 2023
Dunn School Group Leader Fumiko Esashi has been awarded a BBSRC Pioneer Award to support her research on centromere evolution.
New technique shows centromeres are hotspots for DNA breaks
January 2023
Published in Molecular Cell, the Esashi lab demonstrates a new technique for detecting DNA breaks, which they use to show that centromeres are hotspots for DNA breaks.
Three Dunn School academics recognised with Full Professor title
December 2021
Many congratulations to Omer Dushek, Fumiko Esashi and Ulrike Gruneberg We are delighted to announce that three Dunn School group leaders were recognised in this year’s University of Oxford Recognition of Distinction exercise. Omer Dushek is now Professor of Molecular Immunology. His group investigates the immunology of T cell receptor signal integration, at the interface...