Fidelity and processivity of DNA synthesis by DNA polymerase kappa, the product of the human DINB1 gene.
Mammalian DNA polymerase kappa (pol kappa), a member of the UmuC/DinB nucleotidyl transferase superfamily, has been implicated in spontaneous mutagenesis. Here we show that human pol kappa copies undamaged DNA with average single-base substitution and deletion error rates of 7 x 10(-3) and 2 x 10(-3), respectively. These error rates are high when compared to those of most other DNA polymerases. pol kappa also has unusual error specificity, producing a high proportion of T.CMP mispairs and deleting and adding non-reiterated nucleotides at extraordinary rates. Unlike other members of the UmuC/DinB family, pol kappa can processively synthesize chains of 25 or more nucleotides. This moderate processivity may reflect a contribution of C-terminal residues, which include two zinc clusters. The very low fidelity and moderate processivity of pol kappa is novel in comparison to any previously studied DNA polymerase, and is consistent with a role in spontaneous mutagenesis.
Ohashi
E
E
Institute for Virus Research, Kyoto University, Sakyo, Kyoto 606-8507, Japan.
Bebenek
K
K
Matsuda
T
T
Feaver
W J
WJ
Gerlach
V L
VL
Friedberg
E C
EC
Ohmori
H
H
Kunkel
T A
TA
D020137:Base Pair Mismatch; D001483:Base Sequence; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase; D017353:Gene Deletion; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D011506:Proteins / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D000099270:Y-Family DNA Polymerases
D004259:DNA-Directed DNA Polymerase; D011506:Proteins; C404302:POLK protein, human; D000099270:Y-Family DNA Polymerases