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- Title
Mycobacterial Ku and ligase proteins constitute a two-component NHEJ repair machine.
- Authors
Della, Marina; Palmbos, Phillip L; Tseng, Hui-Min; Tonkin, Louise M; Daley, James M; Topper, Leana M; Pitcher, Robert S; Tomkinson, Alan E; Wilson, Thomas E; Doherty, Aidan J
- Abstract
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.
- Publication
Science (New York, N.Y.), 2004, Vol 306, Issue 5696, p683
- ISSN
1095-9203
- Publication type
Journal Article
- DOI
10.1126/science.1099824