Non-homologous end joining (WP438)
Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. NHEJ is referred to as "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homologous recombination, which requires a homologous sequence to guide repair. NHEJ involves binding of the KU heterodimer to double-stranded DNA ends, recruitment of DNA-PKcs (MRX complex in yeast), processing of ends, and recruitment of the DNA ligase IV (LIG4)-XRCC4 complex, which brings about ligation. NHEJ typically utilizes short homologous DNA sequences called microhomologies to guide repair. These microhomologies are often present in single-stranded overhangs on the ends of double-strand breaks. When the overhangs are perfectly compatible, NHEJ usually repairs the break accurately. Imprecise repair leading to loss of nucleotides can also occur, but is much more common when the overhangs are not compatible. Inappropriate NHEJ can lead to translocations and telomere fusion, hallmarks of tumor cells. NHEJ is evolutionarily conserved throughout all kingdoms of life and is the predominant double-strand break repair pathway in mammalian cells. Adapted from [http://en.wikipedia.org/wiki/Non-homologous_end_joining Wikipedia], [https://www.genome.jp/dbget-bin/www_bget?pathway+hsa03450 KEGG] and [http://repairtoire.genesilico.pl/Pathway/8/ REPAIRtoire]. This pathway is part the [https://assays.cancer.gov/available_assays?wp_id=WP438 CPTAC Assay Portal].
AuthorsThomas Kelder , Alex Pico , Kristina Hanspers , Martijn Van Iersel , Chetan1 , Zahra Roudbari , Denise Slenter , Finterly Hu , and Lars Willighagen
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- DNA methylation of ARHGAP30 is negatively associated with ARHGAP30 expression in lung adenocarcinoma, which reduces tumor immunity and is detrimental to patient survival (2021).
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Pathway Ontologynon-homologous end joining pathway of double-strand break repair DNA repair pathway
- DNA double-strand break repair: all’s well that ends well. Wyman C, Kanaar R. Annu Rev Genet. 2006;40:363–83. PubMed Europe PMC Scholia