Flexibility in the order of action and in the enzymology of the nuclease, polymerases, and ligase of vertebrate non-homologous DNA end joining: relevance to cancer, aging, and the immune system.
Nonhomologous DNA end joining (NHEJ) is the primary pathway for repair of double-strand DNA breaks in human cells and in multicellular eukaryotes. The causes of double-strand breaks often fragment the DNA at the site of damage, resulting in the loss of information there. NHEJ does not restore the lost information and may resect additional nucleotides during the repair process. The ability to repair a wide range of overhang and damage configurations reflects the flexibility of the nuclease, polymerases, and ligase of NHEJ. The flexibility of the individual components also explains the large number of ways in which NHEJ can repair any given pair of DNA ends. The loss of information locally at sites of NHEJ repair may contribute to cancer and aging, but the action by NHEJ ensures that entire segments of chromosomes are not lost.
Lieber
Michael R
MR
USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Rm 5428, Los Angeles, CA 90089-9176, USA. lieber@usc.edu
Lu
Haihui
H
Gu
Jiafeng
J
Schwarz
Klaus
K
D000220:Adaptation, Biological / Q000235:genetics*; D000375:Aging / Q000235:genetics* / Q000502:physiology; D000818:Animals; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004260:DNA Repair / Q000235:genetics* / Q000502:physiology; D045643:DNA Repair Enzymes / Q000378:metabolism / Q000502:physiology; D051747:DNA-Activated Protein Kinase / Q000378:metabolism / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000502:physiology*; D003851:Deoxyribonucleases / Q000235:genetics / Q000502:physiology*; D004720:Endonucleases; D006801:Humans; D007107:Immune System / Q000201:enzymology* / Q000378:metabolism; D017578:Immunoglobulin Class Switching / Q000235:genetics; D008954:Models, Biological; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology; D011995:Recombination, Genetic; D050441:VDJ Exons / Q000235:genetics; D014714:Vertebrates / Q000235:genetics
D004268:DNA-Binding Proteins; C508551:NHEJ1 protein, human; D009687:Nuclear Proteins; C101467:XRCC4 protein, human; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D004259:DNA-Directed DNA Polymerase; C426344:DCLRE1C protein, human; D003851:Deoxyribonucleases; D004720:Endonucleases; D011088:DNA Ligases; D045643:DNA Repair Enzymes; D000072481:DNA Ligase ATP