Simon Boulton

DSB Repair Metabolism Laboratory

DNA is a highly reactive molecule that is susceptible to damage. Fortunately, cells have evolved specialised repair processes that are remarkably efficient in correcting specific types of DNA damage.

Failure to correctly repair DNA damage will lead to mutagenic change, which can contribute to ageing and cancer. Indeed, defects in genes that repair DNA damage are the underlying cause of a number of hereditary ageing/cancer predisposition syndromes such as Fanconi anemia and Blooms.

The focus of my lab is to identify new DNA repair genes, understand how they work in DNA repair in mitotic and meiotic cells and determine how defects in these processes contribute to human diseases such as cancer.

We hope that our work will provide an improved understanding of how DNA repair works and how, when DNA repair is compromised, it contributes to cancer/ageing and or infertility disorders in humans.

DNA replication and telomere functions of RTEL1

DNA replication and telomere functions of RTEL1

Selected publications

Taylor MRG, Špírek M, Chaurasiya KR, Ward JD, Carzaniga R, Yu S, Egelman EH, Collinson LM, Rueda D, Krejci L & Boulton SJ (2015). Rad51 paralogs remodel pre-synaptic Rad51 filaments to stimulate homologous recombination. Cell, 162, 271-86.

Hořejší Z, Stach L, Flower TG, Joshi D, Flynn H, Skehel JM, O'Reilly N, Ogrodowicz RW, Smerdon SJ & Boulton SJ (2014). Phosphorylation-dependent PIH1D1 interactions define substrate specificity of the R2TP co-chaperone complex.Cell Rep. 2014.03.013 

Adelman CA, Lolo RL, Birkbak NJ, Murina O, Matsuzaki K, Horejsi Z, Parmar K, Borel V, Skehel JM, Stamp G, D'Andrea A, Sartori AA, Swanton C & Boulton SJ. HELQ promotes RAD51 paralogue-dependent DNA repair to avert germ cell loss and tumorigenesisNature. 2013;502(7471):381-4 

Chapman JR, Barral P, Vannier J-B, Borel-V, Steger M, Tomas-Loba A, Sartori AA, Adams I, Batista FD, Boulton SJ. RIF1 is essential for 53BP1-dependent non-homologous end joining and suppression of DNA double strand break resectionMolecular Cell, 2013;49: 858-71 

Vannier JB, Sandhu S, Petalcorin MIR, Wu X, Nabi Z, Ding H & Boulton SJ (2013). RTEL1 is a replisome-associated helicase that promotes genome and telomere replicationScience. 342:239-242 

Gari K., Leon Ortiz AM, Borel-Vannier V, Flynn H, Skehel JM & Boulton SJ (2012). MMS19 links cytoplasmic FeS cluster assembly to DNA metabolismScience. 337:243-5 

Vannier J-B, Petalcorin MIR, Pavicic-Kaltenbrunner V, Ding H & Boulton SJ (2012). RTEL1 dismantles T-loops and counteracts telomeric G4-DNA to maintain telomere integrityCell, 149:795-806

Hořejší Z, Takai H, Collis SJ, Flynn H, Maslen S, Skehel J.M, de Lange T and Boulton SJ (2010). CK2 phospho-dependent binding of R2TP complex to Tel2 regulates PIKK stabilityMolecular Cell 39:839-50 

Ward JD, Muzzini DM, Petalcorin MI, Martinez-Perez E, Martin JS, Plevani P, Cassata G, Marini F, Boulton SJ (2010). Overlapping mechanisms promote postsynaptic RAD-51 filament disassembly during meiotic double-strand break repairMolecular Cell 37:259-72. 

Youds JL, Mets DG, McIlwraith MJ, Martin JS, Ward JD, ONeil NJ, Rose AM, West SC, Meyer BJ, Boulton SJ (2010). RTEL-1 enforces meiotic crossover interference and homeostasisScience 327:1254-8 

Ahel D, Horejsí Z, Wiechens N, Polo SE, Garcia-Wilson E, Ahel I, Flynn H, Skehel M, West SC, Jackson SP, Owen-Hughes T, Boulton SJ (2009). Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodelling enzyme ALC1Science 325:1240-3. 

Ahel I, Ahel D, Matsusaka T, Clark AJ, Pines J, Boulton SJ, West SC. PBZ: a novel poly(ADP-ribose)-binding zinc finger motif in DNA repair/checkpoint proteinsNature. 451:81-85 

Barber LJ, Youds JL, Ward JD, McIlwraith MJ, O'Neil NJ, Petalcorin MI, Martin JS, Collis SJ, Cantor SB, Auclair M, Tissenbaum H, West SC, Rose AM, Boulton SJ (2008). RTEL1 maintains genomic stability by suppressing inappropriate recombinationCell 135:261-71. 

 

Simon Boulton

simon.boulton@crick.ac.uk
+44 (0)20 379 61774

  • Qualifications and history
  • 1998 PhD, University of Cambridge, UK
  • 1998 HFSP and EMBO Postdoctoral Fellow, Harvard Medical School, USA
  • 2002 Established lab at the London Research Institute, Cancer Research UK
  • 2015 Group Leader, The Francis Crick Institute, London, UK