Martin Reijns Research Group

Research in a Nutshell

DNA damage not only threatens genome stability and cell survival, but can also lead to inflammation and mutagenesis. This is relevant to autoinflammatory diseases, ageing and cancer. It is therefore important to understand the consequences of how different cells respond to different types of DNA damage. Our aim is to determine the mechanisms by which damage leads to specific types of mutations or causes activation of the innate immune system (inflammation).

Deoxyribonucleotides are the canonical building blocks of DNA, but ribonucleotides (the building blocks of RNA) can be incorporated by the enzymes that perform DNA synthesis. A key area of interest is how, when and where ribonucleotides are incorporated into DNA; how, when and where they are removed (or not); and how this affects the genome and the cell. Absence of RNase H2, an enzyme essential for initiating their removal through Ribonucleotide Excision Repair (RER), causes DNA damage, inflammatory signalling and an increase in small deletions characteristic of the cancer mutational signature ID4.

We use molecular biology, biochemistry, NGS and bioinformatics applied to budding yeast, mammalian cells and transgenic mouse models to investigate the interplay between DNA damage, repair, mutagenesis and inflammation, with a focus on genome-embedded ribonucleotides.

1. Signatures of TOP1 transcription-associated mutagenesis in cancer and germline. Reijns MAM, Parry DA, Williams TC, Nadeu F, Hindshaw RL, Rios Szwed DO, Nicholson MD, Carroll P, Boyle S, Royo R, Cornish AJ, Xiang H, Ridout K, Schuh A, Aden K, Palles C, Campo E, Stankovic T, Taylor MS, Jackson AP. Nature. 2022; 1–9. doi:10.1038/s41586-022-04403-y
2. CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions. Zimmermann M, Murina O, Reijns MAM, Agathanggelou A, Challis R, Tarnauskaitė Ž, Muir M, Fluteau A, Aregger M, McEwan A, Yuan W, Clarke M, Lambros MB, Paneesha S, Moss P, Chandrashekhar M, Angers S, Moffat J, Brunton VG, Hart T, de Bono J, Stankovic T, Jackson AP, Durocher D. Nature. 2018;559(7713):285-289. doi:10.1038/s41586-018-0291-z
3. cGAS surveillance of micronuclei links genome instability to innate immunity. Mackenzie KJ, Carroll P, Martin CA, Murina O, Fluteau A, Simpson DJ, Olova N, Sutcliffe H, Rainger JK, Leitch A, Osborn RT, Wheeler AP, Nowotny M, Gilbert N, Chandra T, Reijns MAM, Jackson AP. Nature. 2017; 548(7668):461-465. doi:10.1038/nature23449
4. Lagging-strand replication shapes the mutational landscape of the genome. Reijns MAM, Kemp H, Ding J, de Procé SM, Jackson AP, Taylor MS. Nature. 2015; 518: 502–506. doi:10.1038/nature14183
5. Enzymatic removal of ribonucleotides from DNA is essential for mammalian genome integrity and development. Reijns MAM, Rabe B, Rigby RE, Mill P, Astell KR, Lettice LA, Boyle S, Leitch A, Keighren M, Kilanowski F, Devenney PS, Sexton D, Grimes G, Holt IJ, Hill RE, Taylor MS, Lawson KA, Dorin JR, Jackson AP. Cell. 2012; 149(5):1008-22. doi:10.1016/j.cell.2012.04.011

Full publication list can be found on Research Explorer: Martin Reijns - Research output - University of Edinburgh Research Explorer

• Professor Martin Taylor, MRC HGU, University of Edinburgh
• Professor Yanick Crow, MRC HGU, University of Edinburgh
• Dr Carolina Uggenti, MRC HGU, University of Edinburgh
• Professor Min Ae Lee-Kirsch, Dresden University, Germany
• Professor Grant Stewart, University of Birmingham
• Professor Nick Gilbert, MRC HGU, University of Edinburgh
• Professor Ian Holt, Biodonostia Health Research Institute, Spain
• Professor Antonella Spinazzola, University College London
• Dr Konrad Aden, Kiel University, Germany
• Professor Dan Durocher, University of Toronto, Canada
• Professor Tatjana Stankovic, University of Birmingham
• Dr Roger Woodgate, NIHCD, USA
• Professor Anna Kajaste-Rudnitski, University of Pavia, Italy
• Professor Eva Petermann, University of Birmingham
• Dr Erik Debler, Thomas Jefferson University, USA
• Dr Aline Marnef, CBI, Toulouse, France
• Dr Nic Robertson, IGC, University of Edinburgh
• Dr Rebekah Tillotson, IGC, University of Edinburgh
• Dr Anke Roelofs, IGC, University of Edinburgh
• Professor Cosimo De Bari, IGC, University of Edinburgh
• Ms Manisha Ahuja, Newcastle University
• Professor Sophie Hambleton, Newcastle University
• Dr Tom Deegan, MRC HGU, University of Edinburgh
• Dr Luke Boulter, IGC, University of Edinburgh
• Dr Sylvie Noordermeer, Leiden University, The Netherlands

• Medical Research Council