A Biochemically Defined System for Mammalian Nonhomologous DNA End Joining
| Autor: | Haihui Lu, Myron F. Goodman, Klaus Schwarz, Osamu Koiwai, Brigette Tippin, Chih-Lin Hsieh, Michael R. Lieber, Yunmei Ma, Noriko Shimazaki |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
DNA Repair
DNA polymerase Molecular Sequence Data Oligonucleotides DNA-Activated Protein Kinase DNA-Directed DNA Polymerase Protein Serine-Threonine Kinases Models Biological DNA polymerase delta 03 medical and health sciences 0302 clinical medicine Sequence Homology Nucleic Acid Escherichia coli Animals Ku Autoantigen Molecular Biology 030304 developmental biology chemistry.chemical_classification 0303 health sciences DNA ligase Base Sequence Models Genetic biology DNA replication Nuclear Proteins Antigens Nuclear DNA Processivity Cell Biology Endonucleases Molecular biology DNA polymerase lambda Protein Structure Tertiary Cell biology DNA-Binding Proteins DNA ligase IV complex chemistry 030220 oncology & carcinogenesis Mutation biology.protein DNA polymerase mu DNA Damage Protein Binding |
| Zdroj: | Molecular Cell. 16(5):701-713 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2004.11.017 |
| Popis: | Nonhomologous end joining (NHEJ) is a major pathway in multicellular eukaryotes for repairing double-strand DNA breaks (DSBs). Here, the NHEJ reactions have been reconstituted in vitro by using purified Ku, DNA-PK(cs), Artemis, and XRCC4:DNA ligase IV proteins to join incompatible ends to yield diverse junctions. Purified DNA polymerase (pol) X family members (pol mu, pol lambda, and TdT, but not pol beta) contribute to junctional additions in ways that are consistent with corresponding data from genetic knockout mice. The pol lambda and pol mu contributions require their BRCT domains and are both physically and functionally dependent on Ku. This indicates a specific biochemical function for Ku in NHEJ at incompatible DNA ends. The XRCC4:DNA ligase IV complex is able to ligate one strand that has only minimal base pairing with the antiparallel strand. This important aspect of the ligation leads to an iterative strand-processing model for the steps of NHEJ. |
| Databáze: | OpenAIRE |
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