The molecular basis and disease relevance of non-homologous DNA end joining

Bailin Zhao; Eli Rothenberg; Dale A Ramsden; Michael R Lieber

doi:10.1038/s41580-020-00297-8

The molecular basis and disease relevance of non-homologous DNA end joining

Nat Rev Mol Cell Biol. 2020 Dec;21(12):765-781. doi: 10.1038/s41580-020-00297-8. Epub 2020 Oct 19.

Authors

Bailin Zhao^{1

2

3

4

5}, Eli Rothenberg⁶, Dale A Ramsden⁷, Michael R Lieber^{8

9

10

11

12}

Affiliations

¹ Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
² Department of Biochemistry & Molecular Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
³ Department of Molecular Microbiology & Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
⁴ USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
⁵ Molecular and Computational Biology Section, Department of Biological Sciences, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, USA.
⁶ Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, USA.
⁷ Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA. dale_ramsden@med.unc.edu.
⁸ Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA. lieber@usc.edu.
⁹ Department of Biochemistry & Molecular Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA. lieber@usc.edu.
¹⁰ Department of Molecular Microbiology & Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA. lieber@usc.edu.
¹¹ USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA, USA. lieber@usc.edu.
¹² Molecular and Computational Biology Section, Department of Biological Sciences, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, USA. lieber@usc.edu.

Abstract

Non-homologous DNA end joining (NHEJ) is the predominant repair mechanism of any type of DNA double-strand break (DSB) during most of the cell cycle and is essential for the development of antigen receptors. Defects in NHEJ result in sensitivity to ionizing radiation and loss of lymphocytes. The most critical step of NHEJ is synapsis, or the juxtaposition of the two DNA ends of a DSB, because all subsequent steps rely on it. Recent findings show that, like the end processing step, synapsis can be achieved through several mechanisms. In this Review, we first discuss repair pathway choice between NHEJ and other DSB repair pathways. We then integrate recent insights into the mechanisms of NHEJ synapsis with updates on other steps of NHEJ, such as DNA end processing and ligation. Finally, we discuss NHEJ-related human diseases, including inherited disorders and neoplasia, which arise from rare failures at different NHEJ steps.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
DNA Breaks, Double-Stranded*
DNA End-Joining Repair / physiology*
DNA Repair / physiology*
Disease / genetics*
Genetic Diseases, Inborn / genetics
Humans
Neoplasms / genetics
Neoplasms / pathology
Signal Transduction / genetics

Abstract

Publication types

MeSH terms

Grants and funding