The frameshift infidelity of human DNA polymerase lambda. Implications for function.
DNA polymerase lambda (Pol lambda) 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 lambda. The results indicate that the average single-base deletion error rate of Pol lambda is higher than those of other mammalian polymerases. In fact, unlike other DNA polymerases, Pol lambda generates single-base deletions at average rates that substantially exceed base substitution rates. Moreover, the sequence specificity for single-base deletions made by Pol lambda is different from that of other DNA polymerases and reveals that Pol lambda 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 lambda in non-homologous end-joining. This may include non-homologous end-joining of strand breaks resulting from DNA damage, because Pol lambda has intrinsic 5',2'-deoxyribose-5-phosphate lyase activity.
Bebenek
Katarzyna
K
Laboratory of Molecular Genetics and Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA.
Garcia-Diaz
Miguel
M
Blanco
Luis
L
Kunkel
Thomas A
TA
D001483:Base Sequence; D001665:Binding Sites; D019951:DNA Polymerase beta / Q000235:genetics* / Q000502:physiology*; D004260:DNA Repair; D016368:Frameshift Mutation; D017353:Gene Deletion; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding
C415367:DNA polymerase beta2; D019951:DNA Polymerase beta