Double-strand DNA break repair

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 as Rad52, 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.

Homologous recombination

Figure 1: Diagram of homologous recombination.