Towards an Atomic Understanding of Double-Strand Break Repair: Crystal Structure of Human RAD52 Protein
Abstract
This is the first year report for 3 year Pre-doctoral trainee ship award (June 2000, DMADl7-OO-l-0469) and following describes the progress made last 12 months. This research project focuses on the study of human RAD52 (hRAD52) protein and the ultimate goal is to determine the crystal structure of hRAD52. The hRAD52 plays a central role in the repair of DNA double strand breaks (DSBs). Historically identified in yeast by its role in resistance to ionization radiation, hRAD52 has shown to be interacting with many proteins in the recombination based DSBs repair pathway 1. Although it is clear that RAD52 plays a crucial role in DSBs repair, the exact biochemical function of this protein has remained elusive. It has been shown that the RADS2 epistasis groups of genes are responsible for the repair of DSBs. These genes include RAD5O-57, RPA, MkEl 1, and XRS2 and those have been identified based on their sensitivity to ionizing radiation I. Recent findings indicate that there is direct link between DNA DSB pathway and breast cancer 2. (3ermline mutations in the BRCAl and BRCA2 genes are susceptible to breast cancer and ovarian cancer. hRAD5 1 interacts with tumor-suppressor gene products, BRCA2 and BRCAl 2,3. This indicates BRCA2 may be an essential cofactor in the RADS 1 dependent DNA DSB pathway. hRAD52 and hRAD5 1 may act together at the ssDNA-binding step of DSB repair 4, 5. The three-dimensional structure of hRAD52 will contribute to the understanding of regulation and function of hRAD52. Specifically, interaction surfaces on hRAD52 that interact with hRAD5 1 will be visualized.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA396405
Entities
People
- Gloria Borgstahl
- Wasantha K. Ranatunga
Organizations
- University of Toledo