DNA double-strand breaks (DSBs) often lead to incompatible chromosome ends that can be repaired by the complex, poorly understood, non-homologous end-joining (NHEJ) pathway. Now, reporting in Science, Aidan Doherty and colleagues have shown that, in Mycobacterium tuberculosis, just two proteins can carry out the gamut of processes that are required for NHEJ.

The researchers subjected the M. tuberculosis DNA ligase Mt-Lig to a range of in vitro assays to assess its usefulness in DNA repair. In a dazzling display of versatility, Mt-Lig showed competence as an RNA polymerase, a combined DNA polymerase and ligase, an RNA primase, a terminal transferase and even showed 3′→5′ single-stranded-DNA exonuclease activity. Interestingly, this resourceful protein used NTPs — the nucleotides that are incorporated into RNA — to correctly fill in an in vitro DSB. Also, co-transfection of Mt-Lig with another mycobacterial repair protein, Mt-Ku, restored NHEJ in a DNA-repair mutant yeast.

Referring to Mt-Lig, Steve Kowalczykowski from the University of California, USA, remarked that it was “...just amazing how there are so many activities in one protein”, and was curious to find out “...how its component parts can catalyze so many different events typically separated in eukaryotes” (The Scientist, 25 October 2004). And, corresponding author, Aiden Doherty, from the University of Sussex, UK, highlighted the intriguing prospect that “...RNA could be used to repair DSBs probably as a short-term measure.”

As well as shedding light on the NHEJ processes, molecular biologists are relishing the prospect of using this all-in-one repair kit to facilitate DNA cloning.