The Role of PHRF1 in DNA damage/repair

The Plant homeodomain (PHD) finger is a type of reader domain found in over 100 human proteins, and interacts with methylated or unmodified versions of H3K4. Moreover past studies have implicated a PHD finger containing protein (PHRF1) as a tumor enhancer/suppressor in lung vs. breast cancer. We study PHRf1, a protein that has PHD and RING finger domains, to observe how altering said domains affects the DNA damage/repair pathways involved in cancer therapy or more generally how its presence/absence affects DNA damage repair. Peptide microarrays as well as Domain microarrays were used as protein-histone binding tests to determine the protein of interest PHRF1. Colorectal cancer cells were chosen as model cells due to their higher expression of PHRF1. Several constructs were generated using CRISPR technology with alterations to the reading domains. The constructs had DNA damage induced (double stranded breaks) via Zeocin (DNA damaging chemotherapeutic drug) and tested for levels of damage/repair using Western blots. Results showed that ΔPHRF1 cells are more susceptible to DNA damage suggesting PHRF1 might play a role in DNA damage repair. Results indicate that our gene of interest could be explored as a route for cancer therapy since cancer cells are often less effective in repairing DNA damage as compared to noncancerous cells.