Fidelity and processivity of DNA synthesis by DNA polymerase kappa, the product of the human DINB1 gene.

Abstract:

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.

Polymerases:

Topics:

Fidelity, Nucleotide Incorporation, Exonuclease Activity

Status:

new topics/pols set partial results complete validated

Results:

Polymerase Reference Property Result Context
Human Pol kappa Ohashi E2000 3-5' Exonuclease (proofreading) No
Human Pol kappa Ohashi E2000 Cloned or native Native organism
Human Pol kappa Ohashi E2000 Tagged Yes
Human Pol kappa Ohashi E2000 Tag Name GST, His
Human Pol kappa Ohashi E2000 Nucleotide Substitution Rate 0.0058 errors/bp
Human Pol kappa Ohashi E2000 Full length or truncated Full length
Human Pol kappa Ohashi E2000 Processivity 25bp
Human Pol kappa Ohashi E2000 Gap Filling Yes
Pol Kappa (exo-) Ohashi E2000 3-5' Exonuclease (proofreading) No
Pol Kappa (exo-) Ohashi E2000 Cloned or native Cloned in E. coli
Pol Kappa (exo-) Ohashi E2000 Nucleotide Substitution Rate 0.0074 errors/bp
Pol Kappa (exo-) Ohashi E2000 Full length or truncated Full length
Pol Kappa (exo-) Ohashi E2000 Processivity 5bp
Pol Kappa (exo-) Ohashi E2000 Gap Filling Yes
Human Pol eta Ohashi E2000 Nucleotide Substitution Rate 0.035 errors/bp
Human Pol beta Ohashi E2000 Nucleotide Substitution Rate 0.00067 errors/bp
Human Pol alpha Ohashi E2000 Nucleotide Substitution Rate 0.00016 errors/bp
Human Pol delta Ohashi E2000 Nucleotide Substitution Rate 1E-05 errors/bp

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