The research project led by Pauline Lescaux and Kristijan Ramadan (https://www.imm.ox.ac.uk/research/research-groups/ramadan-group-1) led to the discovery of a new mechanism of DNA repair, nucleophagy. We have shown that the repair of DNA-protein crosslinks (DPCs) which is initiated in the nucleus by the adaptor protein TEX264 and the ATPase segregase p97, is completed in the lysosomes. We show that DPCs are extruded through the nuclear envelope and taken up by the lysosome through the process of TEX264-mediated signaling. The repair pathway is dissected in vitro and in cultured cells, and we also show that it is relevant at the organismal level using zebrafish animal model. Additionally, we show that our findings are relevant for the chemotherapy protocols in colorectal cancer patients. Official press releases as well as articles published in local newspapers are available at the following links:

https://www.ox.ac.uk/news/2024-09-13-study-discovers-new-process-cells-repair-dna-damage

September 2024

https://www.ntu.edu.sg/news/detail/study-discovers-new-process-for-cells-to-repair-dna-damage

https://theindependent.sg/ntu-oxford-team-uncovers-new-process-for-cells-to-repair-dna-damage/

https://www.vecernji.hr/vijesti/hrvatski-znanstvenici-otkrili-proces-kojim-se-poboljsava-postojeca-terapija-za-karcinom-debelog-crijeva-1799191

Link to access the original article: https://www.sciencedirect.com/science/article/pii/S0092867424009115