Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2023
Höfundar / Authors: Thejus B Venkatesh, Drífa Hrund Guðmundsdóttir, Linda Viðarsdóttir, Stefán Þórarinn Sigurðsson
Starfsvettvangur / Affiliations: 1. Háskóli Íslands
Kynnir / Presenter: Thejus B Venkatesh
MITF is a transcription factor with a well-established function in melanocytes and melanoma, but little is known about the non-melanocyte-specific function of the protein. The genome is constantly damaged due to extracellular and intracellular sources. Among different kinds of DNA damage, DNA double-strand breaks (DSBs) are considered particularly genotoxic with a high risk of causing genome instability. MITF has been shown to interact with DNA DSB repair proteins in previous publications and we observe similar interactions of MITF with DNA repair proteins using mass spectrometry. In addition, we find MITF to be co-localized with DNA repair proteins at sites of DNA DSBs suggesting that MITF might have a role in DNA DSB repair, possibly independent of the protein's transcriptional activity. We also show that knocking down MITF reduces the DSB repair efficiency compared to the control. In this study we use the osteosarcoma cell line U2OS as our research model, to uncover the non-melanocyte-specific role of MITF. MITF A-isoform is the predominantly expressed isoform in U2OS cells as opposed to the M-isoform in the melanocyte lineage. Our mass spectrometry data shows that the A-isoform has a stronger affinity to DNA DSB repair proteins compared to the M-isoform, suggesting an isoform-specific function of MITF. We hypothesize that MITF-A might be involved in DNA repair by directly binding to the DNA break site or interacting with DNA repair proteins at the break site.