Molecular Cell
Volume 19, Issue 3, 5 August 2005, Pages 357-366
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Article
A Gradient of Template Dependence Defines Distinct Biological Roles for Family X Polymerases in Nonhomologous End Joining

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Summary

Three Pol X family members have been linked to nonhomologous end joining (NHEJ) in mammals. Template-independent TdT promotes diversity during NHEJ-dependent repair of V(D)J recombination intermediates, but the roles of the template-dependent polymerases μ and λ in NHEJ remain unclear. We show here that pol μ and pol λ are similarly recruited by NHEJ factors to fill gaps when ends have partially complementary overhangs, suggesting equivalent roles promoting accuracy in NHEJ. However, only pol μ promotes accuracy during immunoglobulin kappa recombination. This distinctive in vivo role correlates with the TdT-like ability of pol μ, but not pol λ, to act when primer termini lack complementary bases in the template strand. However, unlike TdT, synthesis by pol μ in this context is primarily instructed by a template from another DNA molecule. This apparent gradient of template dependence is largely attributable to a small structural element that is present but different in all three polymerases.

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