An Overview of the Molecular Mechanisms of Recombinational DNA Repair

Abstract

Recombinational DNA repair is a universal aspect of DNA metabolism and is essential for genomic integrity. It is a template-directed process that uses a second chromosomal copy (sister, daughter, or homolog) to ensure proper repair of broken chromosomes. The key steps of recombination are conserved from phage through human, and an overview of those steps is provided in this review. The first step is resection by helicases and nucleases to produce single-stranded DNA (ssDNA) that defines the homologous locus. The ssDNA is a scaffold for assembly of the RecA/RAD51 filament, which promotes the homology search. On finding homology, the nucleoprotein filament catalyzes exchange of DNA strands to form a joint molecule. Recombination is controlled by regulating the fate of both RecA/RAD51 filaments and DNA pairing intermediates. Finally, intermediates that mature into Holliday structures are disjoined by either nucleolytic resolution or topological dissolution.

Figure 1.

Molecular mechanism of recombinational DNA repair. The steps comprising recombinational DNA repair are schematically illustrated (see text for details). Some steps are unidirectional commitments (e.g., resection) and are shown with single arrows, whereas others are reversible (e.g., DNA pairing and invasion), and are shown with two arrows. In the latter case, the forward step is shown to the left of the arrows, and the backward step is shown to the right. Intermediates from the biochemical steps are channeled into the repair pathways shown. DSB, double-stranded DNA break; NHEJ, nonhomologous end joining; SSA, single-strand DNA annealing; SDSA, synthesis-dependent strand annealing. The outcome of each pathway, crossover or noncrossover, is indicated. (From Cejka et al. 2010b; adapted, with permission, from the authors.)