A new DNA repair pathway discovery by the Ramadan group
Members from Kristijan Ramadan’s group in the CRUK/MRC Oxford Institute of Radiation Oncology have discovered a mechanism of how cells remove covalently attached proteins from DNA, known as DNA-protein crosslinks (DPCs). DPCs are toxic lesions and if they are not removed lead to genomic instability and cancer. However, the mechanism regarding how cells remove and repair DPCs was unknown until now. The Group has found that SPARTAN (SPRTN) is a DNA-dependent metalloprotease which cleaves covalently attached proteins (DPCs) from DNA and thus allows unperturbed DNA replication. A defect in SPARTAN metalloprotease activity leads to genomic instability, premature ageing and cancer.
In summary, the Group has discovered a DNA repair pathway, namely (DNA replication coupled DNA-protein crosslink repair pathway) which is essential to protect us from toxic DNA-protein crosslinks and consequently from accelerated ageing and cancer.
The Group have recently had an article published in the November 2016 Molecular Cell publication and the article can be viewed on-line.
Congratulations to Bruno Vaz and Marta Popovic who are the first authors on this article along with other group members from the Ramadan group as well as other collaborators who contributed to this discovery.