Mycobacterial Ku and ligase proteins constitute a two-component NHEJ repair machine

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

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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.

Item Type: Article
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
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