Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2025
Erindi/veggspjald / Talk/poster E76
Höfundar / Authors: Thejus B Venkatesh, Guðjón Ólafsson, Younes Farhangi Barooji, Fjóla Dögg Aðalsteinsdóttir, Drífa Hrund Guðmundsdóttir, Linda Viðarsdóttir, Eiríkur Steingrímsson, Kumar soumyajit, Thorkell Gudjónsson, Stefán Sigurðsson
Starfsvettvangur / Affiliations: University of Iceland
Kynnir / Presenter: Thejus Venkatesh
Genomic stability is vital for normal cell function, and disruptions can lead to cancer and other diseases. Genomic instability can arise from DNA damage, replication stress, or a combination of both. MITF is a transcription factor with a well-established function in melanocyte biology; however, little is known about the non-melanocyte-specific functions of the protein. 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 predominantly expressed in U2OS cells as opposed to the M-isoform in the melanocyte lineage. We found that MITF-A depletion leads to increased 53BP1 foci formation, p53 accumulation, and signs of replication stress. Differentially expressed genes upon MITF-A isoform depletion show downregulation of genes associated with DNA replication and DNA repair. Protein-protein interaction analysis by Mass spectrometry revealed that MITF-A interacts strongly with proteins involved in DNA replication and repair, including RPA and PARP1, compared to MITF-M. Consistently, single-molecular C-trap assays show that MITF-A, but not MITF-M, stably binds RPA-coated ss-DNA. Using QIBC and DNA fiber assay, we are investigating MITF-A in safeguarding replication fork stability under stress. These findings identify a lineage-independent, isoform-specific role for MITF-A in maintaining genome integrity, suggesting broader functions for MITF in cancer biology beyond melanoma.