Analysis of RNF138 Interaction with RAD51D and Basis for Discovery of RNF138 E3 Ligase Inhibitors

Description:

Reference #: 00837

Invention Description:

Deficiencies in DNA damage response and repair pathways that manage DNA double-strand breaks (DSBs) are associated with cancer susceptibility. RAD51D, a member of the RAD51 protein family, is required for homology-directed repair of both DNA DSBs and interstrand crosslinks. The protein also maintains chromosome and telomere integrity. RAD51D participates in the "BRCA2 complex" and interacts directly with RAD51C and XRCC2.

Invention Description:

Dr. Douglas Pittman has identified RNF138, a mediator of homology-directed DNA DSB repair that functions by making direct interactions with RAD51D. RNF138 is novel in having both a RING finger E3 ubiquitin ligase domain (RING) and an ubiquitin interaction motif (UIM). Ubiquitin signaling is essential for DNA double-strand break repair.

RNF138 was shown to interact specifically with RAD51D. Further, it was determined that RNF138 knockdown impairs DNA damage repair, RNF138 depletion confers increased chromosome instability, and RNF138 expression is increased in cancer cell lines.

Potential Applications:

The RNF138 mediator is a potential cancer susceptibility marker or possible chemotherapeutic target.

Advantages and Benefits:

Inhibiting RNF138 activity will be an effective therapeutic strategy to increase the sensitivity of cancer cells to chemotherapeutic agents that induce DSBs. The benefit will be improved treatment of cancer and decreased chemotherapy side effects.

Patent Information:
Title App Type Country Serial No. Patent No. File Date Issued Date Expire Date Patent Status
Methods for Affecting Homology-Directed DNA Double Stranded Break Repair Utility United States 13/105,258 8,563,243 5/11/2011 10/22/2013 10/21/2031  
For Information, Contact:
Technology Commercialization
University of South Carolina
technology@sc.edu
Inventors:
Douglas Pittman
Brian Yard
Keywords:
© 2018. All Rights Reserved. Powered by Inteum