Terminating DNA Repair Through Disruption of the SUMO Cycle
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Dr. Jianghai Wang in Dr. Yuan Chen?s lab at City of Hope is investigating the role of SUMO (Small Ubiquitin-like Modifier) proteins in DNA repair through the study of the SUMO cycle. We know the basic cycle that SUMO takes during DNA repair consisting of a SUMO specific protease to activate SUMO by attaching to an E1 enzyme. Then, by transesterification, SUMO joins with an E2 SUMO enzyme. The target protein can be conjugated to SUMO with the help of an E3 ligase. Deconjugation of the SUMO~target bond is facilitated by a SUMO-specific protease which finishes the cycle. However, we do not know the active sites of SUMO and its substrates that would help us understand how this cycle works. In order to determine what may cause a disruption in the SUMO cycle, we are mutating the E1 and E2 substrates to confirm the active sites and running assays to determine if the mutated proteins react the same in the cycle. If we are able to find the mutation that alters the SUMO cycle, we could then try to find some way to alter the protein in cancerous cells in the human body to stop DNA repair after its been damaged by traditional cancer therapies.