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Mycobacterial Ku and ligase proteins constitute a two-component NHEJ repair machine.
journal contributionposted on 2023-06-07, 19:52 authored by Marina Della, Phillip L Palmbos, Hui-Min Tseng, Louise M Tonkin, James M Daley, Leana M Topper, Robert S Pitcher, Alan E Tomkinson, Thomas E Wilson, Aidan DohertyAidan Doherty
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.
Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
NotesAD directed the research and was the corresponding author. This work showed how NHEJ repairs DNA breaks by reconstiuting complete DNA end-joining both in vivo and in vivo. Also the first time a eukaryotic repair pathway had been fully complemented by a prokaryotic pathway in vivo.
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