Polymerases in nonhomologous end joining: building a bridge over broken chromosomes

Repair of double-strand breaks in chromosomal DNA is essential. Unfortunately, a paradigm central to most DNA repair pathways--damaged DNA is replaced by polymerases, by using an intact, undamaged complementary strand as a template--no longer works. The nonhomologous end joining (NHEJ) pathway nevertheless still uses DNA polymerases to help repair double-strand breaks. Bacteria use a member of the archaeo-eukaryal primase superfamily, whereas eukaryotes use multiple members of the polymerase X family. These polymerases can, depending on the biologic context, accurately replace break-associated damage, mitigate loss of flanking DNA, or diversify products of repair. Polymerases specifically implicated in NHEJ are uniquely effective in these roles: relative to canonic polymerases, NHEJ polymerases have been engineered to do more with less.