Modulation of DNA repair systems by the essential melanocyte transcription factor Microphthalmia

The exponential increase of melanoma incidence is ultimately linked to UV exposure during childhood. We hypothesize that genomic stability is regulated by the melanocyte master regulator MITF which is essential for the development, survival and differentiation of melanocytes. Its master role is exemplified by the direct transcriptional regulation of Bcl-2, CDK2 and Tyrosinase. MITF expression is maintained throughout the transformation of melanocytes to melanoma, which is highly resistant to chemotherapeutics. Genome wide expression analysis suggest a regulatory role of MITF in nucleotide excision repair and DNA…