Repair of DNA Double Strand Breaks

Patrick Sung
University of Texas Health Sciences Center, San Antonio
R01ES7061

Background: Studies using yeast have identified homologous recombination and nonhomologous endjoining as the two mechanisms for repairing DNA double strand breaks (DSBs). The repair of DSBs is critical for the maintenance of genomic stability. Defects in the mechanisms for repair of DSBs have been linked with inherited human cancer-prone syndromes such as ataxia telangiectasia-like disorder and Nijemegen breakage syndrome. These investigators conducted studies to determine the major genes and their protein products responsible for these events.

Advance: These studies demonstrate that the complex formed by Rad50, Mre11, and Xrs2 proteins promotes intermolecular DNA joining by DNA ligase IV and its associated protein Lif1. The results also demonstrate that the protein complex-mediated intermolecular DNA joining is stimulated by Hdf1/Hdf2, a heterodimer of two proteins analogous to the eucaryotic heterodimer Ku70/Ku80. These studies reveal the specific interplay between the complexes and that the system is homologous to the system in eucaryotic cells.

Implication: The importance of these findings is that they provide major insight into how cells repair DSBs and that the systems for repair are similar among lower and higher organisms. DSBs can occur from a variety of environmental agents such as ionizing radiation and chemical exposures. Understanding how the repair processes work will eventually enable scientists to discover how they are perturbed in disease states.

Citation: Chen L, Trujillo K, Ramos W, Sung P, Tomkinson AE. Promotion of Dnl4-catalyzed DNA end-joining by the Rad50/Mre11/Xrs2 and Hdf1/Hdf2 complexes. Mol Cell. 2001 Nov;8(5):1105-15.