DNA ligase III

Abstract

extra view 3636 Cell Cycle volume 10 issue 21 Lig1 and Lig4 are found throughout eukaryotes. Lig1 is considered to be the critical ligase during replication of the nuclear genome, while Lig4 is critical for the repair of double-strand breaks (DSBs) by nonhomologous end joining (NHEJ). Lig3 has been implicated both in nuclear DNA repair and in mitochondrial genome maintenance. 3,4 Although Lig3 has a more restricted phylogenetic distribution in eukaryotes than the other two ligases, it is found more broadly in eukaryotic groups than originally thought, as will be discussed below. Lig3 is Essential for Cellular Viability due to its Role in Mitochondria Recent work using both cell comple-mentation and tissue-specific deletion in the animal has shed light on the role of Lig3. 5-7 Lig3-null mouse embryos die at ~8.5 dpc and previous attempts to generate Lig3-null cells were unsuccessful, 8 suggesting that Lig3 is required for cell survival. To directly determine whether Lig3 is an essential gene in cells, we developed a pre-emptive complementa-tion strategy in mouse embryonic stem (ES) cells (Fig. 1). For this approach, a Lig3 KO/cKOneo+ cell line was constructed to contain one Lig3-null allele and one conditional allele in which loxP sites flank several Lig3 exons and a drug selection marker. 7 A wild-type Lig3 transgene was stably integrated into the Lig3 KO/cKOneo+ cells; Cre recombinase was then expressed to transform the endogenous Lig3 conditional allele into a second null allele. With this approach, drug sensitive clones d na ligases are crucial for most dna transactions, including dna replication, repair and recombi-nation. recently, dna ligase iii (lig3) has been demonstrated to be crucial for cell survival due to its catalytic function in mitochondria. this review summarizes these recent results and reports on a hitherto unappreciated widespread phylogenetic presence of lig3 in eukaryotes, including in some organisms before the divergence of meta-zoa. analysis of these putative lig3 homologs suggests that many of them are likely to be found in mitochondria and to be critical for mitochondrial function.