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4qze

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Mouse Tdt, F401A mutant, in complex with a DSB substrate, C-G base pair

Structural highlights

4qze 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 2.25Å
Ligands:	, ,
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^[1]

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

References

↑ Gouge J, Rosario S, Romain F, Poitevin F, Beguin P, Delarue M. Structural basis for a novel mechanism of DNA bridging and alignment in eukaryotic DSB DNA repair. EMBO J. 2015 Apr 15;34(8):1126-42. doi: 10.15252/embj.201489643. Epub 2015 Mar, 11. PMID:25762590 doi:http://dx.doi.org/10.15252/embj.201489643