Della, M., Palmbos, P. L., Tseng, H. M., Tonkin, L. M., Daley, J. M., Topper, L. M., Pitcher, R. S., Tomkinson, A. E., Wilson, T. E. and Doherty, A. J. (2004) Mycobacterial Ku and ligase proteins constitute a two-component NHEJ repair machine. Science, 306 (5696). pp. 683-5. ISSN http://eprints.sussex.ac.uk/570/Full text not available from this repository.
In mammalian cells, repair of DNA double-strand breaks (DSBs) by nonhomologous end-joining (NHEJ) is critical for genome stability. Although the end-bridging and ligation steps of NHEJ have been reconstituted in vitro, little is known about the end-processing reactions that occur before ligation. Recently, functionally homologous end-bridging and ligation activities have been identified in prokarya. Consistent with its homology to polymerases and nucleases, we demonstrate that DNA ligase D from Mycobacterium tuberculosis (Mt-Lig) possesses a unique variety of nucleotidyl transferase activities, including gap-filling polymerase, terminal transferase, and primase, and is also a 3' to 5' exonuclease. These enzyme activities allow the Mt-Ku and Mt-Lig proteins to join incompatible DSB ends in vitro, as well as to reconstitute NHEJ in vivo in yeast. These results demonstrate that prokaryotic Ku and ligase form a bona fide NHEJ system that encodes all the recognition, processing, and ligation activities required for DSB repair.
|Keywords:||Bacterial Proteins/chemistry/genetics/ metabolism DNA/ metabolism DNA Damage DNA Ligases/chemistry/genetics/ metabolism DNA Nucleotidyltransferases/chemistry/metabolism DNA Primase/chemistry/metabolism DNA Repair DNA-Directed DNA Polymerase/chemistry/metabolism Exonucleases/chemistry/metabolism Mutation Mycobacterium tuberculosis/genetics/ metabolism Polymerase Chain Reaction Protein Structure, Tertiary Recombination, Genetic Research Support, Non-U.S. Gov't Saccharomyces cerevisiae/genetics|
|Schools and Departments:||School of Life Sciences|
|Depositing User:||Aidan Doherty|
|Date Deposited:||27 Nov 2006|
|Last Modified:||30 Nov 2012 16:50|
|Google Scholar:||91 Citations|