Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2019

Erindi/veggspjald / Talk/poster E41

The role of MITF in the response to DNA double strand breaks

Höfundar / Authors: Drífa Hrund Guðmundsdóttir (1), Stefán Þ. Sigurðsson (2), Þorkell Gupjónsson (3)

Starfsvettvangur / Affiliations: Háskóli Íslands

Kynnir / Presenter: Drífa Hrund Guðmundsdóttir

MITF is best known for its role as the master regulator of melanocytes. The protein also plays a key role in melanoma, where it functions as an oncogene and is often referred to as a driver of melanoma progression.
Among different types of DNA damage, DNA double strand breaks (DSBs) are considered particularly genotoxic, as both DNA strands are severed and the risk of losing genetic material is high. The cell has two main pathways to repair DSBs; non-homologous end joining (NHEJ) and homologous recombination (HR). In addition to these highly efficient repair pathways there are two alternative more error prone pathways; microhomology-mediated end joining (MMEJ) and single-strand annealing (SSA).
Studies have shown that MITF interacts with key regulators of the DNA DSB response, including Ku70/80 and DNA-Pk of the NHEJ repair pathway and BRCA2 of the HR repair pathway.
We show that after MITF depletion the number of spontaneous DSBs are increased. We also show that MITF is co-localized with repair proteins at sites of damage in a subset of cells. Our results also suggest that knocking down MITF negatively affects the efficiency DSB repair. This negative effect has been observed in DSB repair with the NHEJ and HR repair pathways.