Characterization of FANCD2

Abstract

FANCD2 is a nuclear protein that functions as the central player in the FA Signaling Pathway. As this pathway repairs DNA damage, it has become a unique model system to study cancer. Previously, our lab identified an unrecognized form of FANCD2, FANCD2-V2. Therefore, studies on FANCD2 are likely a mix of both FANCD2 isoforms, leaving much to be explored. In this thesis we characterized FANCD2-V2. We found FANCD2-V2 is expressed in non-cancer and lower stage cancer tissues compared to FANCD2-V1, the well-known form in the field. Additionally, the production of one FANCD2 transcript over the other is due to the methylation status of a proximal or distal polyadenylation site. We next examined the function of FANCD2-V2 and found FANCD2-V2 responds earlier to DNA damage through an interaction with cytoplasmic protein, TFG. Loss of such interaction results in a tumorigenic phenotype. Our findings contribute to our current knowledge of FANCD2 and the FA Signaling Pathway by identifying a function and binding partner specific to FANCD2-V2.