Crystal structure of a DinB family error-prone DNA polymerase from Sulfolobus solfataricus.
A new group of error-prone DNA polymerases overcomes the blockage posed to normal DNA replication by damaged template bases, suggesting an active site with a loose, flexible pocket that accommodates aberrant DNA structures. We have determined a 2.8 A resolution crystal structure of the Sulfolobus solfataricus Dbh protein, a DNA translesion polymerase closely related to Escherichia coli DNA polymerase IV and human polymerase kappa. A high error rate is observed for the Dbh polymerase in a range of 10(-2)-10(-3) for all 12 base substitution mispairs. The crystal structure of Dbh reveals an overall architecture resembling other DNA polymerases but has unique features that are likely to contribute to error-prone synthesis, including -1 frameshifting mutations.
Silvian
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Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
Toth
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EA
Pham
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Goodman
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MF
Ellenberger
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D000595:Amino Acid Sequence; D019843:Archaeal Proteins; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D002384:Catalysis; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D019951:DNA Polymerase beta / Q000737:chemistry*; D004259:DNA-Directed DNA Polymerase; D029968:Escherichia coli Proteins; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D016944:Sulfolobus / Q000201:enzymology*; D019914:Taq Polymerase / Q000378:metabolism; D000099270:Y-Family DNA Polymerases
D019843:Archaeal Proteins; D001426:Bacterial Proteins; D019951:DNA Polymerase beta; D004259:DNA-Directed DNA Polymerase; D029968:Escherichia coli Proteins; D011506:Proteins; D019914:Taq Polymerase; C094399:DinB protein, E coli; C436950:Dbh protein, Sulfolobus solfataricus; C404302:POLK protein, human; D000099270:Y-Family DNA Polymerases