Scientists from IQFR have revealed the inhibition mechanism of UDG, a key enzyme for DNA repair. The work has been developed in collaboration with scientists from CBMSO (CSIC-UAM).

UDG is the first enzyme acting in a specific DNA repair pathway, called BER, where it detects uracil in DNA. Once detected, uracil is removed and subsequent enzymes within the BER pathway continue the process. Several proteins have been identified capable to inhibit UDG, among them p56 encoded by different phages probably as a defence mechanism.

p56 is a DNA mimic protein that blocks the UDG active site. The structure of the complex showed a specific recognition pattern between UDG and p56 that explains the lack of cross-reactivity among p566 and other DNA binding proteins. Therefore, our results shed light onto the UDG-blocking mechanism used by some viruses to proliferate into the host cell. Moreover, they pave the way to the potential use of p56 as antiviral agent against some infectious caused by herpes and poxvirus.

Publication:
José Ignacio Baños-Sanz, Laura Mojardín, Julia Sanz-Aparicio, José M. Lázaro, Laurentino Villar, Gemma Serrano-Heras, Beatriz González*, and Margarita Salas*.
Crystal structure and functional insights into uracil-DNA glycosylase inhibition by phage ϕ29 DNA mimic protein p56
Nucl. Acids Res. 2013 doi:10.1093/nar/gkt395