Congratulations to Karim Labib, who has just been awarded a £2 million Research Programme award from Cancer Research UK, to study new mechanisms that preserve genome integrity during the final stages of chromosome replication in animal cells. Karim’s lab previously used budding yeast to study DNA replication termination, but the new award, which will commence in the spring of 2018, is based on pioneering work with the worm Caenorhabditis elegans by Dr. Remi Sonneville in Karim’s group (Sonneville et al, 2017, Nat. Cell Biol., 19, 468-479). Remi showed that the ubiquitin ligase CUL-2LRR-1 controls disassembly of the DNA replication machinery (the ‘replisome’) at the end of chromosome replication in animal cells. However, in the absence of CUL-2LRR-1, the replisome persists until mitosis but is then disassembled by a new pathway that requires the worm orthologoue of a protein mutated in various human cancers. The new award will support work to investigate the molecular mechanisms of these two pathways. This work is important in the context of cancer research, since simultaneous inactivation of the two replisome disassembly pathways causes synthetic lethality, suggesting that inhibitors of CUL-2LRR-1 might kill cancer cells in which the mitotic disassembly pathway is inactive.

Commenting on this work, Karim said “I am very grateful to CRUK for their support, which will enable us to expand our work with animal cells and hopefully gain insight into an important process that is defective in particular human cancers, suggesting future approaches to new therapies”. Dario Alessi, Director of the MRC PPU, added “securing this very prestigious and sought-after grant award from cancer research UK is a wonderful achievement for Karim and his lab. It will enable them to undertake exciting and important fundamental research to much better understand how termination of DNA replication is controlled and how this process may be disrupted in cancer”.