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Título : Lack of sugar discrimination by human Pol µ requires a single glycine residue
Autor : Ruiz, José F. ; Juárez, Raquel; García, Miguel Ángel; Terrados, Gloria; Picher, Ángel J. ; González-Barrera, Sergio; Fernández de Henestrosa, Antonio; Blanco, Luis
Palabras clave : DNA polymerase mu
Fecha de publicación : 2003
Editor: Oxford University Press
Citación : Nucleic Acids Research, 2003, Vol. 31, No. 15, 4441-4449
Resumen: DNA polymerase mu (Pol µ) is a novel family X DNA polymerase that has been suggested to play a role in micro-homology mediated joining and repair of double strand breaks. We show here that human Pol µ is not able to discriminate against the 2'-OH group of the sugar moiety. It inserts rNTPs with an efficiency that is <10-fold lower than that of dNTPs, in sharp contrast with the >1000-fold discrimination characteristic of most DNA-dependent DNA polymerases. The lack of sugar discrimination by Pol µ is demonstrated by its ability to add rNTPs to both DNA and RNA primer strands, and to insert both deoxy- and ribonucleotides on growing nucleic acid chains. 3D-modelling of human Pol µ based on the available Pol ß and TdT structural information allowed us to predict candidate residues involved in sugar discrimination. Thus, a single amino acid substitution in which Gly433 residue of Pol µ was mutated to the consensus tyrosine present in Pol ß, produced a strong increase in the discrimination against ribonucleotides. The unusual capacity to insert both rNTPs and dNTPs will be discussed in the context of the predicted roles of Pol µ in DNA repair
Versión del editor: http://dx.doi.org/10.1093/nar/gkg637
URI : http://hdl.handle.net/10261/7784
DOI: 10.1093/nar/gkg637
ISSN: 0305-1048 (print)
1362-4962 (online)
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