Maintenance of genome stability in stem cells
The repair of damaged DNA is essential in all cells to ensure that the fidelity of the genome is maintained and to prevent mutations arising. This is of particular importance in stem cells, as mutations will not only effect that individual cell but the many millions of progeny derived from it.
Our research focuses on how germ cells maintain genomic stability. These stem cells ultimately give rise to either sperm or oocytes. When these gametes come together they produce a new organism with new germ cells, therefore allowing endless propagation of a species. The maintenance of the genetic integrity in the germline is of critical importance to ensure the faithful transmission of the genome from one generation to the next. Failure to accurately maintain genome stability in germ cells has catastrophic consequences for the offspring and to the survival of the species. Despite their importance and unique lifecycle little is known about germ cells repair genome damage.
We use a combination of mouse genetics and state of the art molecular biology tools to investigate the mechanisms that prevent mutagenesis in the germline.
- Crossan, G.P., van der Weyden, L., Rosado, I.V., Langevin, F., Gaillard, P.H., McIntyre, R.E., Sanger Mouse Genetics Project, Gallagher, F., Kettunen, M.I., Lewis, D.Y., Brindle, K., Arends, M.J., Adams, D.J. and Patel K.J. (2011)
Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemia.
Nature Genetics 43: 147-152
- Garaycoechea, J.I., Crossan, G.P., Langevin, F., Daly, M., Arends, M.J. and Patel, K.J. (2012)
Genotoxic consequences of endogenous aldehydes on mouse haematopoietic stem cell function.
Nature 489: 571-575
- Oberbeck, N., Langevin F., King, G., Wind, N., Crossan G.P. and Patel K.J. (2014)
Maternal aldehyde elimination during pregnancy preserves the fetal genome.
Molecular Cell 55: (6): 807 – 817
- Ross Hill
- Gonçalo Oliveira
- Jonathan Ribeiro