Homologous recombination

Gene

Replication protein A

Non-homologous end joining

DNA repair

DNA damage

Mutagenesis

Nijmegen breakage syndrome

Ataxia-telangiectasia

Mutation

Genetics

DNA mismatch repair

Homologous chromosome

DNA replication

Homology directed repair

Transcription factor

Biology

DNA-binding protein

Cell biology

Chromosoma

DNA double-strand breaks arise accidentally upon exposure of DNA to radiation and chemicals or result from faulty DNA metabolic processes. DNA breaks can also be introduced in a programmed manner, such as during the maturation of the immune system, meiosis, or cancer chemo- or radiotherapy. Cells have developed a variety of repair pathways, which are fine-tuned to the specific needs of a cell. Accordingly, vegetative cells employ mechanisms that restore the integrity of broken DNA with the highest efficiency at the lowest cost of mutagenesis. In contrast, meiotic cells or developing lymphocytes exploit DNA breakage to generate diversity. Here, we review the main pathways of eukaryotic DNA double-strand break repair with the focus on homologous recombination and its various subpathways. We highlight the differences between homologous recombination and end-joining mechanisms including non-homologous end-joining and microhomology-mediated end-joining and offer insights into how these pathways are regulated. Finally, we introduce noncanonical functions of the recombination proteins, in particular during DNA replication stress.

Main steps in DNA double-strand break repair: an introduction to homologous recombination and related processes