My lab is interested in the mechanisms that alleviate arrested DNA replication and the impact their loss has on mutagenesis and on the maintenance of epigenetic memory through the recycling of histones during replication.
Replication can be arrested by DNA damage or by naturally occurring DNA secondary structures. We are particularly interested in translesion synthesis (TLS), which is mediated by specialised DNA polymerases and which is required for replication of both DNA damage and a particular secondary structure called a G quadruplex. Although TLS is potentially mutagenic it plays a critical role in normal cells and understanding its control is central to understanding cell transformation.
We study these processes using the powerful combination of vertebrate somatic cell genetics coupled with biochemical, biophysical and advanced optical microscopy techniques to monitor the molecular choreography of proteins and DNA at sites of stalled replication.
The green and red portions each reflect 20 minutes of DNA synthesis. DNA damage has been added
during the second (red) labelling period in the lower panel resulting in replication fork stalling.
Selected Papers
- Šviković, S., et. al. (2019)
R-loop formation during S phase is restricted by PrimPol-mediated repriming.
EMBO J. 38(3): pii: e99793, doi:10.15252/embj.201899793. - Lerner, L.K. and Sale, J.E. (2019)
Replication of G quadruplex DNA.
Genes (Basel) 10(2): pii E95. doi: 10.3390/genes10020095. - Guilbaud, G., Murat, P. et al. (2017)
Local epigenetic reprogramming induced by G quadruplex ligands.
Nature Chemistry 9(11): 1110-1117. doi:10.1038/nchem.2828. - Svikovic, S. and Sale J.E. (2017)
The effects of replication stress on S phase histone management and epigenetic memory.
J. Mol. Biol. 429: 2011-2029. - Schiavone, D., Jozwiakowski, S. et al. (2016)
PrimPol is required for replicative tolerance of G quadruplexes in vertebrate cells.
Molecular Cell 61: 161-169.
Group Members
- Colette Baxter
- Alastair Crisp
- Guillaume Guilbaud
- Jedrzej Jaworski
- Christopher Mellor
- Pierre Murat
- Consuelo Perez
- Sasa Svikovic
- Lucy Walker