The frameshift infidelity of human DNA polymerase λ: Implications for function

Abstract

DNA polymerase λ (Pol λ) is a member of the Pol X family having properties in common with several other mammalian DNA polymerases. To obtain clues to possible functions in vivo, we have determined the fidelity of DNA synthesis by human Pol λ. The results indicate that the average single-base deletion error rate of Pol λ is higher than those of other mammalian polymerases. In fact, unlike other DNA polymerases, Pol λ generates single-base deletions at average rates that substantially exceed base substitution rates. Moreover, the sequence specificity for single-base deletions made by Pol λ is different from that of other DNA polymerases and reveals that Pol λ readily uses template-primers with limited base pair homology at the primer terminus. This ability, together with an ability to fill short gaps in DNA at low dNTP concentrations, is consistent with a role for mammalian Pol λ in non-homologous end-joining. This may include non-homologous end-joining of strand breaks resulting from DNA damage, because Pol λ has intrinsic 5′,2′-deoxyribose-5-phosphate lyase activity.