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Determination of RAD52 and replication fork DNA complex


EMSL Project ID
51258

Abstract

RAD52 is an emerging target for drug discovery targeting DNA repair-deficient tumors. The exact cellular functions and structural mechanisms of RAD52, however, remain unresolved. This proposed project is built around our current model, whereby two undecameric rings of RAD52 bind to the stalled replication fork. RAD52 then remodels the fork into a structure refractory to fork regression enzymes. Our objective is to visualize this structure. We seek time on the Titan Krios and 200kV Talos Artica to obtain high resolution 3D reconstructions of undecameric rings of the RAD52 DNA repair protein (Aim1) and of the RAD52 rings bound to a synthetic DNA structure mimicking stalled replication fork (Aim2). Our preliminary data (the 2D class averages of RAD52 rings are consistent with the expected structure, but show preferred orientation) both support feasibility of the project and highlight the need for Titan Krios access to achieve the high resolution RAD52-fork structure.

Project Details

Start Date
2020-01-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Maria Spies
Institution
University of Iowa

Co-Investigator(s)

Nicholas Schnicker
Institution
University of Iowa

Team Members

Theo Humphreys
Institution
Oregon Health & Science University

Irina El Khoury
Institution
Environmental Molecular Sciences Laboratory