ABSTRACT
The integrity of the phosphodiester backbone of DNA is disrupted as a consequence of normal DNA metabolism. During DNA replication, the lagging strand is synthesized as a series of short Okazaki fragments that must be linked together to generate an intact strand. In addition, there are DNA rearrangements such as V(D) J recombination in mammals and mating type switching in yeast that are initiated by a site-specific DNA double strand break (DSB) that must be rejoined to restore genomic integrity. DNA is also subject to attack by endogenous and exogenous DNA damaging agents. Under these circumstances, DNA strand breaks may be introduced either directly by the action of the agent such as ionizing radiation or as a consequence removal of the DNA lesion by the DNA excision repair pathways. Irrespective of how they are caused, it is critical for genomic stability that DNA strand breaks are efficiently joined. In the cell, this task is performed by a group of enzymes known as DNA ligases. As expected from the involvement of DNA strand breaks in many different DNA transactions, cells mutated in a DNA ligase-encoding gene often exhibit a pleiotropic phenotype (1-4).
