An intrinsic 5′-deoxyribose-5-phosphate lyase activity in DNA polymerase beta from Leishmania infantum supports a role in DNA repair

Abstract Leishmania infantum is a parasitic protozoan which infects humans. This paper reports the expression in Escherichia coli and purification of the L. infantum gene product ( AF182167 ), as well as its characterization as a DNA polymerase beta (Polβ)-like, template-dependent DNA repair enzyme, with a metal preference for Mn 2+ over Mg 2+ . As is the case with mammalian Polβ and DNA polymerase lambda (Polλ), L. infantum DNA polymerase beta (Li Polβ) prefers gapped-DNA substrates having a 5′-phosphate end, in agreement with its role in DNA repair reactions. Purified Li Polβ also displayed a 5′-deoxyribose-5-phosphate (dRP) lyase activity, consistent with a β-elimination mechanism. The concerted action of dRP lyase and DNA polymerization activities of Li Polβ on a uracil-containing DNA suggests its participation in “single-nucleotide” base excision repair (BER). Analysis of Li Polβ DNA polymerization activity at different stages of the L. infantum infective cycle supports a role for Li Polβ in nuclear DNA repair after the oxidative damage occurring inside the macrophage.