DNA Joining in Mammalian Cells

Abstract

Since their discovery almost 30 years ago, DNA ligases have been used extensively as reagent enzymes. Joining of DNA single-strand breaks and double-strand breaks can be achieved efficiently by employing over-produced microbial DNA ligases, and this is a key step in recombinant DNA research. The facile sealing of DNA strand interruptions with commercially obtained enzymes in vitro may have generated the impression that DNA ligation is a simple, unregulated process in vivo. This is not likely to be the case. Instead, recent work on DNA-joining activities in mammalian cell nuclei indicates that DNA ligation efficiency is reg-ulated at several evels, including transcriptional nd posttranslational control of DNA ligase activity, and is influenced by the occurrence of separate protein activators and inhibitors of DNA ligases, the presence of multiple DNA ligases in cell nuclei, and the exist-ence of other proteins uch as poly(ADP-ribose) poly-merase that bind tightly at DNA chain breaks. Current work on these topics is summarized below; a recent extensive review on mammalian DNA ligases contains references to earlier investigations (Lindahl and Barnes