The DNA in our cells is damaged by natural biological processes and environmental factors every day. Fortunately, the body has effective DNA damage repair machinery that repairs the vast majority of this damage. The most common DNA damage – double-strand breaks – are recognised by the MRE11-RAD50-NSB1 (MRN) protein complex, which binds to the broken DNA and starts the recruitment of other repair factors.
DNA damage repair is an important consideration when selecting cancer therapies. Several treatments, including radiotherapy and some chemotherapies, work by damaging the cancer cell DNA, resulting in cancer cell death. Tumour types that are resistant to these types of treatment may have evolved specific DNA damage repair pathways. Learning more about these pathways may uncover new opportunities for therapeutic targeting.
Ludwig Oxford’s Dr Romuald Binet from Professor Colin Goding’s laboratory has been awarded a Development Fund from the Cancer Research UK Oxford Centre. Working with Professor Kristijan Ramadan (Department of Oncology) and Professor Davide Mazza (IRCCS Ospedale San Raffaele, Milan), Romuald will investigate DNA damage repair in cutaneous melanoma, a radioresistant skin cancer with high levels of DNA damage.
The team have already discovered that, in melanoma, the DNA damage response is modulated by a lineage-specific mechanism that alters the activity of the MRN complex. This project will precisely detail the mechanisms behind the deregulation of the MRN complex in melanoma to provide tissue-specific regulation of the DNA damage response.