The role of NUCKS in DNA repair

Thesis

NUCKS is a vertebrate-specific, extensively post-translationally modified transcriptional regulator whose over- and under- expression is associated with cancer and obesity, respectively. We have previously found that NUCKS protein levels increase in DNA-damaged cells, and other studies have reported DNA damage-dependent NUCKS phosphorylation. However, the full impacts of NUCKS depletion on DNA damage repair has not been established. Addressing this question, we show that NUCKS depletion activates some DNA damage response proteins and might be associated with accumulation of DNA damage in cancer cells. Furthermore, the transcriptional targets for NUCKS are poorly defined. To this end, we couple data from a published ChIP-Seq analysis for NUCKS with a bioinformatics approach to identify genes coexpressed with NUCKS in cancer patient samples and cell lines. We identify a number of genes, including many involved in DNA repair. We correspondingly find that NUCKS-depleted cells express lower levels of these genes and exhibit some hallmarks of their deficiency. Finally, we investigate how NUCKS’ putative transcriptional targets relate to disease, and therefore how NUCKS might be used as a biomarker for disease.

Authors: Hume, S

• DOI: 10.5287/ora-xokwyd0zm
• Type of award: MSc by Research
• Level of award: Masters
• Awarding institution: University of Oxford