Double-strand DNA breaks can be repaired by two main pathways: homologous recombination and non-homologous end-joining. In simple eukaryotes such as yeast, homologous recombination is the main pathway, whereas in higher eukaryotes such as mammals, non-homologous end-joining becomes the main pathway.
Homologous recombination involves several proteins such asRad52, MRE11-Rad50-NSB1 complex, and Rad51. Homologous recombination involves a relationship between damaged DNA and undamaged DNA molecules with which it shares sequence homologies. This undamaged DNA molecule is used as a template for DNA repair.
Steps in homologous recombination are as follows:
Nucleotide restriction of the damage DNA by MRE11-Rad50-NSB1 complex.
Binding of 3'-single-stranded DNA by heptameric ring complex that is formed by Rad52 protein.
Interaction between Rad51 and Rad52 stimulating the DNA strand exchange activity of Rad51.
Rad51 protein catalyzes the strand exchange between damage DNA and template DNA, displacing one strand as D-loop.
Polymerase filling the gap of DNA double-strand breaks.
The resulting structures are resolved by Holiday junction.
Figure 1:Diagram of homologous recombination.