Facoltà di scienze biomediche

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

Ranjha, Lepakshi ; Howard, Sean Michael ; Cejka, Petr

In: Chromosoma, 2018, vol. 127, no. 2 (June), p. 187–214

DNA double-strand breaks arise accidentally upon exposure of DNA to radiation, 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.... More

Add to personal list
    Summary
    DNA double-strand breaks arise accidentally upon exposure of DNA to radiation, 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 sub-pathways. We highlight the differences between homologous recombination and end-joining mechanisms including nonhomologous end-joining and microhomology-mediated end-joining, and offer insights into how these pathways are regulated. Finally, we introduce non-canonical functions of the recombination proteins, in particular during DNA replication stress.