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Kristijan Ramadan and his group published a new article in The EMBO Journal today. The article adds new detail to the story of how our cells repair damage to our DNA.

Dna damage

All day every day cells must detect and repair DNA damage. DNA damage comes in several forms, but the most dangerous and the most relevant for radiotherapy is DNA double strand breaks.

Repairing DNA damage is a team game, with a number of proteins coming together to regulate and carry out the repair. These proteins are vital for the repair, but accumulation of too much of these proteins will cause issues such as genome instability, which can promote both tumour genesis and tumour progression.

RING finger protein 8 (RNF8) is an integral part of the DNA repair process, but it must not be allowed to accumulate in a cell.

Kristijan and his group have uncovered how the cell maintains just the right amount of RNF8. A combination of two proteins, p97 and ATX3 work together to adjust levels of RNF8. Inactivation of the p97-ATX3 combination prevents the cells from regulating the amount of RNF8 and makes the cells very sensitive to radiation.

Since many cancers have evolved to rely heavily on the DNA repair that RNF8 facilitates, this suggests an interesting target for cancer therapy. A target that should hurt cancer cells very much more than healthy ones.

 

 

Abhay Narayan Singh, Judith Oehler, Ignacio Torrecilla, Susan Kilgas, Shudong Li, Bruno Vaz, Claire Guérillon, John Fielden, Esperanza HernandezCarralero, Elisa Cabrera, Iain DC Tullis, Mayura Meerang, Paul R Barber, Raimundo Freire, Jason Parsons, Borivoj Vojnovic, Anne E Kiltie, Niels Mailand, Kristijan Ramadan. (2019) The p97–Ataxin 3 complex regulates homeostasis of the DNA damage response E3 ubiquitin ligase RNF8. EMBO J (2019): e102361

https://www.embopress.org/doi/10.15252/embj.2019102361