%0 Journal Article %T Crystal structures of a template-independent DNA polymerase: murine terminal deoxynucleotidyltransferase %+ Biochimie Structurale %+ Biologie du développement %+ Centre de Recherches sur les Macromolécules Végétales (CERMAV) %A Delarue, M. %A Boulé, J.B. %A Lescar, J. %A Expert-Bezançon, N. %A Jourdan, N. %A Sukumar, N. %A Rougeon, F. %A Papanicolaou, C. %Z This work was supported by Association pour la Recherche contre le Cancer (grant ARC 5470 to M.D.). %< avec comité de lecture %@ 0261-4189 %J EMBO Journal %I EMBO Press %V 21 %N 3 %P 427-439 %8 2002-02-01 %D 2002 %R 10.1093/emboj/21.3.427 %M 11823435 %K crystal structure %K incoming nucleotide %K nucleotidyltransferase %K polymerase %K primer strand %Z Life Sciences [q-bio]Journal articles %X The crystal structure of the catalytic core of murine terminal deoxynucleotidyltransferase (TdT) at 2.35 A resolution reveals a typical DNA polymerase beta-like fold locked in a closed form. In addition, the structures of two different binary complexes, one with an oligonucleotide primer and the other with an incoming ddATP-Co(2+) complex, show that the substrates and the two divalent ions in the catalytic site are positioned in TdT in a manner similar to that described for the human DNA polymerase beta ternary complex, suggesting a common two metal ions mechanism of nucleotidyl transfer in these two proteins. The inability of TdT to accommodate a template strand can be explained by steric hindrance at the catalytic site caused by a long lariat-like loop, which is absent in DNA polymerase beta. However, displacement of this discriminating loop would be sufficient to unmask a number of evolutionarily conserved residues, which could then interact with a template DNA strand. The present structure can be used to model the recently discovered human polymerase mu, with which it shares 43% sequence identity. %G English %L pasteur-04089359 %U https://pasteur.hal.science/pasteur-04089359 %~ PASTEUR %~ UGA %~ CNRS %~ UNIV-GRENOBLE1 %~ CERMAV %~ INC-CNRS