Using rapid protein degradation to determine the effect of RUNX1 loss-of-function on DNA damage accumulation and repair
Mentor Name: Kristy Stengel
The RUNX1 gene is commonly mutated in childhood blood cancers. RUNX1 is a transcription factor, which is a protein that regulates how and when other genes are turned on. While we have assumed that the reason RUNX1 mutations promote cancer is due to its activity in gene regulation, growing literature suggests that RUNX1 may play a less-studied role in preventing the accumulation of DNA damage. To determine whether RUNX1 function in DNA damage responses also contributes to malignancy, we have developed blood cancer models in which we can take the RUNX1 protein away very quickly and assess the effects of RUNX1 loss on DNA repair before RUNX1 loss has time to affect gene expression. This will allow us to begin to understand how RUNX1 mutations lead to increased DNA damage, which has broad implications for disease progression and treatment.
