title: Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining.
abstract: 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 mu and lambda, 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.
authors.affiliation: 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.
authors.forename: Brandi L
authors.initials: BL
authors.lastname: Mahaney
authors.forename: Katheryn
authors.initials: K
authors.lastname: Meek
authors.forename: Susan P
authors.initials: SP
authors.lastname: Lees-Miller
mesh_terms: D000818:Animals; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D051747:DNA-Activated Protein Kinase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D011839:Radiation, Ionizing
chemical_list: D051747:DNA-Activated Protein Kinase; D045643:DNA Repair Enzymes