4qzb

Mouse Tdt in complex with a DSB substrate, C-T base pair

spinqualitylabelsall models 4qzb, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4qzb is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.15Å Ligands: DCT, MG, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TDT_MOUSE Template-independent DNA polymerase which catalyzes the random addition of deoxynucleoside 5'-triphosphate to the 3'-end of a DNA initiator. One of the in vivo functions of this enzyme is the addition of nucleotides at the junction (N region) of rearranged Ig heavy chain and T-cell receptor gene segments during the maturation of B- and T-cells. Publication Abstract from PubMed Eukaryotic DNA polymerase mu of the PolX family can promote the association of the two 3'-protruding ends of a DNA double-strand break (DSB) being repaired (DNA synapsis) even in the absence of the core non-homologous end-joining (NHEJ) machinery. Here, we show that terminal deoxynucleotidyltransferase (TdT), a closely related PolX involved in V(D)J recombination, has the same property. We solved its crystal structure with an annealed DNA synapsis containing one micro-homology (MH) base pair and one nascent base pair. This structure reveals how the N-terminal domain and Loop 1 of Tdt cooperate for bridging the two DNA ends, providing a templating base in trans and limiting the MH search region to only two base pairs. A network of ordered water molecules is proposed to assist the incorporation of any nucleotide independently of the in trans templating base. These data are consistent with a recent model that explains the statistics of sequences synthesized in vivo by Tdt based solely on this dinucleotide step. Site-directed mutagenesis and functional tests suggest that this structural model is also valid for Pol mu during NHEJ. Structural basis for a novel mechanism of DNA bridging and alignment in eukaryotic DSB DNA repair.,Gouge J, Rosario S, Romain F, Poitevin F, Beguin P, Delarue M EMBO J. 2015 Apr 15;34(8):1126-42. doi: 10.15252/embj.201489643. Epub 2015 Mar, 11. PMID:25762590 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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