Nonhomologous DNA end joining in cell‐free systems
Open Access
- 1 November 1999
- journal article
- review article
- Published by Wiley in JBIC Journal of Biological Inorganic Chemistry
- Vol. 265 (3), 849-861
- https://doi.org/10.1046/j.1432-1327.1999.00805.x
Abstract
Double strand DNA breaks are usually caused by ionizing radiation and radiomimetic drugs, but can also occur under normal physiological conditions during double strand break‐induced recombination, such as the rearrangement of T‐cell receptor and immunoglobulin genes during lymphoid development or the mating type switching in yeast. The main repair mechanism for double strand breaks in higher eukaryotes is nonhomologous DNA end joining (NHEJ), which modifies and ligates the two DNA ends without the help of extensive base–pairing interactions for alignment. Defects in double strand break repair are associated with radiosensitivity, predisposition to cancer and immunodeficiency syndromes, and the analysis of the underlying mutations has lead to the identification of several proteins involved in NHEJ. However, these genetic studies have yielded little information on the mechanism of NHEJ, and while some of the protein factors identified possess the expected enzymatic or DNA‐binding activities, the precise role of others remains unclear. Systems for cell‐free NHEJ have been available for over 10 years, but the biochemical analysis of NHEJ has lagged behind the genetic analysis, and not a single protein factor required for NHEJ has been identified by biochemical purification and reconstitution of NHEJ activity. Here I review the current status of in vitro systems for NHEJ, summarize the results obtained and information gained, and discuss the outlook for biochemical approaches to study NHEJ.Keywords
This publication has 79 references indexed in Scilit:
- Rejoining of DNA double‐strand breaks in vitro by single‐strand annealingJBIC Journal of Biological Inorganic Chemistry, 1998
- Implication of DNA-Dependent Protein Kinase in an Early, Essential, Local Phosphorylation Event during End-Joining of DNA Double-Strand Breaks in VitroBiochemistry, 1998
- Non-histone Chromosomal Proteins HMG1 and 2 Enhance Ligation Reaction of DNA Double-Strand BreaksBiochemical and Biophysical Research Communications, 1998
- Double‐strand break repair mediated by DNA end‐joiningGenes to Cells, 1998
- Interaction of DNA-dependent protein kinase with DNA and with Ku: biochemical and atomic-force microscopy studiesThe EMBO Journal, 1997
- The identification and characterization of mammalian proteins involved in the rejoining of DNA double-strand breaks in vitroMutation Research/DNA Repair, 1996
- DNA End Joining by the Klenow Fragment of DNA Polymerase IPublished by Elsevier BV ,1996
- The biochemistry of transcription in eukaryotes: a paradigm for multisubunit regulatory complexesPhilosophical Transactions Of The Royal Society B-Biological Sciences, 1996
- The recognition of DNA damageCurrent Opinion in Genetics & Development, 1996
- A novel pathway of DNA end-to-end joiningCell, 1990