Julian Sale
Vertebrate mutagenesis and DNA damage tolerance
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
- Guilbaud, G., Murat, P. et al. (2017)
Local epigenetic reprogramming induced by G quadruplex ligands.
Nature Chemistry, advanced online publication, 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. - Romanello, M., Schiavone, D. et al. (2016)
H3.3 promotes AID-mediated immunoglobulin V gene diversification.
EMBO J. 35: 1452-64. - Schiavone, D., Jozwiakowski, S. et al. (2016)
PrimPol is required for replicative tolerance of G quadruplexes in vertebrate cells.
Molecular Cell 61: 161-169. - Papadopoulou, C., Guilbaud, G. et al. (2016)
Nucleotide Pool Depletion Induces G-Quadruplex-Dependent Perturbation of Gene Expression.
Cell Reports 13: 2491-503.
Group Members
- Alastair Crisp
- Cara Eldridge
- Guillaume Guilbaud
- Leticia Koch-Lerner
- Daniela Peris
- Benedicte Recolin
- Sasa Svikovic
- Lucy Walker