Date of Award
Master of Science in Biological and Environmental Sciences (MSBES)
Cell and Molecular Biology
Cell & Molecular Biology
Fanconi anemia (FA) is a rare genetic disease characterized by an increased risk for bone marrow failure, leukemia, and premature cancers (Alter et al., 2018). The FA pathway is involved in the repair of DNA damage such as stalled replication forks and DNA interstrand crosslinks (ICL) (Feng et al., 2019; Schlacher et al., 2012). It has been previously seen that under conditions of replication stress, FANCD2, a key protein in the FA pathway, binds to and traverses large actively transcribed genes (Okamoto et al., 2018). Using U2OS 3xFLAG cells we seek to answer the question of why FANCD2 is binding to these genes and if by doing so is it acting as a regulator of transcription? To answer this question, we used a candidate gene approach and chose WWOX and SOX5 and observed if under conditions of aphidicolin (APH), there were changes in their protein and transcript levels. We also observed if the absence of FANCD2 would affect their protein and transcript levels. In this study, it was found that under conditions of replication stress there was little change in both the protein and transcript levels of SOX5 and WWOX. Interestingly, the analysis of an RNA sequencing experiment brought to light the potential for FANCD2 to be involved in neuronal development as it was found that there were significant differences in normalized read counts in a subset of neuronal genes in the absence of FANCD2.
Henrikson, Kathryn, "TRANSCRIPTIONAL REGULATION OF SOX5 AND WWOX BY FANCD2" (2021). Open Access Master's Theses. Paper 1965.