| Repair of DNA double strand breaks (DSBs) by the nonhomologous end joining pathway is made more accurate by the employment of template-dependent gap-filling polymerases. At the inception of this work, the mammalian polymerases employed by the end joining pathway for this role had been unclear. I have found that two mammalian polymerases, polymerase mu (pol mu) and polymerase lambda (pol lambda), form similar specific complexes with end-joining factors, and are equally effective in promoting accurate joining of partially complementary ends through gap-filling synthesis in vitro. Moreover, both polymerases remain effective in this role even when challenged with low deoxynucleotide substrate concentrations, a condition likely to be presented to end joining polymerases in cells. While these in vitro results support a role for both pol mu, and pol lambda in the general repair of DSBs by the end joining pathway, only pol mu increases the accuracy of cellular end joining in the context of V(D)J recombination. I propose a model in which the structure of the ends to be joined dictates which polymerase is used. |
