5d46

Publication Abstract from PubMed

Eukaryotic DNA polymerase of the polX family, such as pol mu and terminal deoxynucleotidyl transferase (TdT), are key components of the non-homologous end-joining or V(D)J recombination machinery, respectively. The established role of TdT is to add random nucleotides during V(D)J recombination. Here we show that TdT also has a templated-polymerase activity, similar to pol mu, in the presence of higher concentrations of a downstream DNA duplex, and performs a micro-homology single base-pair search to align the DNA synapsis. To understand the molecular basis of this alignment, we solve crystal structures of TdT with four DNA strands and study the influence of the 3' protruding end. Two mutations in TdT inspired by sequence alignments with pol mu further improve the templated activity. We propose that both templated and untemplated activities of TdT are needed to explain the distributions of lengths of N regions observed experimentally in T cell receptors and antibodies.

Structural Basis for a New Templated Activity by Terminal Deoxynucleotidyl Transferase: Implications for V(D)J Recombination.,Loc'h J, Rosario S, Delarue M Structure. 2016 Sep 6;24(9):1452-1463. doi: 10.1016/j.str.2016.06.014. Epub 2016 , Aug 4. PMID:27499438^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.