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

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Abstract

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.

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Acknowledgements

We would like to thank the members of the Cejka Laboratory (IRB Bellinzona), Massimo Lopes (University of Zurich), and Kathrin Pieper (Lanzavecchia Laboratory, IRB Bellinzona) for comments on the manuscript. We apologize to colleagues whose work could not be cited due to length constraint.

Funding

The work was supported by grants from the European Research Council (681630) and the Swiss National Science Foundation (31003A_175444) to P.C.

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  1. Lepakshi Ranjha and Sean M. Howard made equal contribution to this work.

Authors and Affiliations

  1. Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland

    Lepakshi Ranjha, Sean M. Howard & Petr Cejka

  2. Department of Biology, Institute of Biochemistry, ETH Zurich, Zurich, Switzerland

    Petr Cejka

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  1. Lepakshi Ranjha
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Ranjha, L., Howard, S. & Cejka, P. Main steps in DNA double-strand break repair: an introduction to homologous recombination and related processes. Chromosoma 127, 187–214 (2018). https://doi.org/10.1007/s00412-017-0658-1

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