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

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 J. Doherty

Research output: Contribution to journalArticlepeer-review

153 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)683-685
Number of pages3
JournalScience
Volume306
Issue number5696
DOIs
StatePublished - Oct 22 2004
Externally publishedYes

ASJC Scopus subject areas

  • General

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