The ubiquitous and essential nature of DNA predicts that enzymes responsibl
e for DNA synthesis evolved early and share a common design and mechanism o
f action. DNA polymerases from many different organisms do exhibit striking
similarities in their overall architecture, the design of the catalytic si
te, and the mechanism of nucleotidyl transfer. In spite of these shared fea
tures, however, DNA polymerases display an astonishing variety in structure
and function, ranging from single subunit enzymes specialized for DNA repa
ir to complex multi-protein holoenzymes responsible for genomic DNA replica
tion. This review uses a few well-characterized model systems to summarize
our current understanding of the workings of DNA polymerases in DNA metabol
ism.