Drosophila models for XPB-related cancer predisposition. Leonie M Quinn¹, Naomi C Mitchell¹, Arjun Chahal¹, Mendis Peter¹, Amandine Michaud-Cartier¹, Ross D Hannan². 1) Anatomy, University of Melbourne, Melbourne, Victoria 3010, Australia; 2) Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne Victoria 3002, AUSTRALIA.

   Mutations that disrupt function of the DNA helicase subunit of the TFIIH transcription factor complex, XPB, have been linked with the human diseases Xeroderma pigmentosum (XP) and Cockayne syndrome (CS). XPB has roles in both DNA-repair and TFIIH-dependent transcription, however, the question of why mutations in the C-terminal domain of XPB results in cancer in some patients, but not others, remains unresolved. Here we correlate XPB/hay mutations with phenotype using a Drosophila model. We demonstrate hay mutants, which lack the conserved C-terminal domain, previously correlated with XPB-related disease, enhances cell and tissue overgrowth in a manner dependent on loss-of-function for the dmyc repressor Hfp. We provide evidence that these larval overgrowth phenotypes are associated with impaired interactions between Hfp and Hay and defective repression of dmyc transcription.