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Título

A specific loop in human DNA polymerase mu allows switching between creative and DNA-instructed synthesis

AutorJuárez, Raquel; Ruiz, José F. ; Nick McElhinny, Stephanie A.; Ramsden, Dale; Blanco, Luis
Palabras claveDNA polymerase mu
Fecha de publicación8-sep-2006
EditorOxford University Press
CitaciónNucleic Acids Research 2006 34(16):4572-4582
ResumenHuman DNA polymerase mu (Polµ) is a family X member that has terminal transferase activity but, in spite of a non-orthodox selection of the template information, displays its maximal catalytic efficiency in DNA-templated reactions. As terminal deoxynucleotidyl transferase (TdT), Polµ has a specific loop (loop1) that could provide this enzyme with its terminal transferase activity. When loop1 was deleted, human Polµ lacked TdT activity but improved DNA-binding and DNA template-dependent polymerization. Interestingly, when loop1 from TdT was inserted in Polµ (substituting its cognate loop1), the resulting chimaera displayed TdT activity, preferentially inserting dGTP residues, but had a strongly reduced template-dependent polymerization activity. Therefore, a specialized loop in Polµ, that could adopt alternative conformations, appears to provide this enzyme with a dual capacity: (i) template independency to create new DNA information, in which loop1 would have an active role by acting as a ‘pseudotemplate’; (ii) template-dependent polymerization, in which loop1 must allow binding of the template strand. Recent in vivo and in vitro data suggest that such a dual capacity could be advantageous to resolve microhomology-mediated end-joining reactions.
Versión del editorhttp://dx.doi.org/10.1093/nar/gkl457
URIhttp://hdl.handle.net/10261/7788
DOI10.1093/nar/gkl457
ISSN0305-1048 (print)
1540-9538 (online)
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