DNA Ligase, T4 - Manual

The search for T4 DNA ligase stemmed from two discoveries during the early 1960s. Meselson and Weigle, and Kellenberger et al. discovered that genetic recombination can occur by the breakage and rejoining of DNA molecules; and Bode and Kaiser discovered that a large fraction of linear DNA from bacteriophage l is rapidly converted to covalently closed duplex circles soon after infection of the host (Meselson and Weigle 1961, Kellenberger et al. 1961, Young and Sinsheimer 1964, and Bode and Kaiser 1965). The race to find the enzyme responsible for this DNA joining activity is evident from the independent and nearly concurrent discovery of DNA ligases by five different laboratories (Gellert 1967, Weiss and Richardson 1967, Olivera and Lehman 1967, Gefter et al. 1967, and Cozzarelli et al. 1967). In 1968, Okazaki et al. discovered another function of DNA ligase: DNA may be replicated discontinuously, and short segments can be joined into continuous strands that make up the chromosome (Lehman 1974). 

Soon after, the widespread distribution in a variety of eukaryotic tissues including rabbit, rat, and lily microsporocytes was observed (Lindahl and Edelman 1968, Tsukada and Ichimura 1971, and Howell and Stern 1971). The gene encoding T4 DNA ligase was cloned by Wilson and Murray in 1979, and the primary structure and genetic organization of T4 DNA ligase was investigated by Armstrong et al. in 1983.

Ligases were critical reagents in molecular cloning development and many applications in DNA biotechnology. There has been a recent rejuvenation in ligase research upon the discovery that most organisms have multiple ligases functioning either in DNA replication or particular repair pathways (Tomkinson et al. 2006, Ellenberger and Tomkinson 2008, Shuman and Glickman 2007, and Shuman 2009).