DNA DSBs (double-strand breaks) are considered the most cytotoxic type of DNA lesion. They can be introduced by external sources such as IR (ionizing radiation), by chemotherapeutic drugs such as topoisomerase poisons and by normal biological processes such as V(D)J recombination. If left unrepaired, DSBs can cause cell death. If misrepaired, DSBs may lead to chromosomal translocations and genomic instability. One of the major pathways for the repair of IR-induced DSBs in mammalian cells is NHEJ (non-homologous end-joining). The main proteins required for NHEJ in mammalian cells are the Ku heterodimer (Ku70/80 heterodimer), DNA-PKcs [the catalytic subunit of DNA-PK (DNA-dependent protein kinase)], Artemis, XRCC4 (X-ray-complementing Chinese hamster gene 4), DNA ligase IV and XLF (XRCC4-like factor; also called Cernunnos). Additional proteins, including DNA polymerases μ and λ, PNK (polynucleotide kinase) and WRN (Werner's Syndrome helicase), may also play a role. In the present review, we will discuss our current understanding of the mechanism of NHEJ in mammalian cells and discuss the roles of DNA-PKcs and DNA-PK-mediated phosphorylation in NHEJ.
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February 2009
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Review Article|
January 16 2009
Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining
Brandi L. Mahaney;
Brandi L. Mahaney
*Department of Biochemistry and Molecular Biology and The Southern Alberta Cancer Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1
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Katheryn Meek;
Katheryn Meek
†College of Veterinary Medicine and Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, U.S.A.
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Susan P. Lees-Miller
Susan P. Lees-Miller
1
*Department of Biochemistry and Molecular Biology and The Southern Alberta Cancer Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1
†College of Veterinary Medicine and Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, U.S.A.
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
February 27 2008
Revision Received:
October 13 2008
Accepted:
October 14 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 417 (3): 639–650.
Article history
Received:
February 27 2008
Revision Received:
October 13 2008
Accepted:
October 14 2008
Citation
Brandi L. Mahaney, Katheryn Meek, Susan P. Lees-Miller; Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining. Biochem J 1 February 2009; 417 (3): 639–650. doi: https://doi.org/10.1042/BJ20080413
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