scholarly journals Kinetic Mechanism of Active Site Assembly and Chemical Catalysis of DNA Polymerase β

Biochemistry ◽  
2011 ◽  
Vol 50 (45) ◽  
pp. 9865-9875 ◽  
Author(s):  
Paul B. Balbo ◽  
Eric Chun-Wei Wang ◽  
Ming-Daw Tsai
Keyword(s):  
Dna Polymerase ◽  
Active Site ◽  
Kinetic Mechanism ◽  
Dna Polymerase Β ◽  
Chemical Catalysis

scholarly journals Structural insights into the promutagenic bypass of the major cisplatin-induced DNA lesion

2020 ◽  
Vol 477 (5) ◽  
pp. 937-951
Author(s):  
Hala Ouzon-Shubeita ◽  
Caroline K. Vilas ◽  
Seongmin Lee
Keyword(s):  
Dna Polymerase ◽  
Active Site ◽  
Cisplatin Resistance ◽  
Structural Basis ◽  
Abasic Site ◽  
Dna Polymerase Β ◽  
Dna Lesion ◽  
Human Dna ◽  
Optimal Conformation ◽  
Structural Insights

The cisplatin-1,2-d(GpG) (Pt-GG) intrastrand cross-link is the predominant DNA lesion generated by cisplatin. Cisplatin has been shown to predominantly induce G to T mutations and Pt-GG permits significant misincorporation of dATP by human DNA polymerase β (polβ). In agreement, polβ overexpression, which is frequently observed in cancer cells, is linked to cisplatin resistance and a mutator phenotype. However, the structural basis for the misincorporation of dATP opposite Pt-GG is unknown. Here, we report the first structures of a DNA polymerase inaccurately bypassing Pt-GG. We solved two structures of polβ misincorporating dATP opposite the 5′-dG of Pt-GG in the presence of Mg2+ or Mn2+. The Mg2+-bound structure exhibits a sub-optimal conformation for catalysis, while the Mn2+-bound structure is in a catalytically more favorable semi-closed conformation. In both structures, dATP does not form a coplanar base pairing with Pt-GG. In the polβ active site, the syn-dATP opposite Pt-GG appears to be stabilized by protein templating and pi stacking interactions, which resembles the polβ-mediated dATP incorporation opposite an abasic site. Overall, our results suggest that the templating Pt-GG in the polβ active site behaves like an abasic site, promoting the insertion of dATP in a non-instructional manner.

scholarly journals Minor Groove Interactions at the DNA Polymerase β Active Site Modulate Single-base Deletion Error Rates

2000 ◽  
Vol 275 (36) ◽  
pp. 28033-28038 ◽  
Author(s):  
Wendy P. Osheroff ◽  
William A. Beard ◽  
Shang Yin ◽  
Samuel H. Wilson ◽  
Thomas A. Kunkel
Keyword(s):  
Dna Polymerase ◽  
Active Site ◽  
Minor Groove ◽  
Error Rates ◽  
Dna Polymerase Β ◽  
Single Base ◽  
Single Base Deletion

scholarly journals Mapping of the 5′-2-Deoxyribose-5-phosphate Lyase Active Site in DNA Polymerase β by Mass Spectrometry

2000 ◽  
Vol 275 (14) ◽  
pp. 10463-10471 ◽  
Author(s):  
Leesa J. Deterding ◽  
Rajendra Prasad ◽  
Gregory P. Mullen ◽  
Samuel H. Wilson ◽  
Kenneth B. Tomer
Keyword(s):  
Mass Spectrometry ◽  
Dna Polymerase ◽  
Active Site ◽  
Dna Polymerase Β

8-OxodGTP Incorporation by DNA Polymerase β Is Modified by Active-Site Residue Asn279†

Biochemistry ◽  
2000 ◽  
Vol 39 (5) ◽  
pp. 1029-1033 ◽  
Author(s):  
Holly Miller ◽  
Rajendra Prasad ◽  
Samuel H. Wilson ◽  
Francis Johnson ◽  
Arthur P. Grollman
Keyword(s):  
Dna Polymerase ◽  
Active Site ◽  
Active Site Residue ◽  
Dna Polymerase Β

scholarly journals Structures of DNA Polymerase β with Active-Site Mismatches Suggest a Transient Abasic Site Intermediate during Misincorporation

2008 ◽  
Vol 30 (3) ◽  
pp. 315-324 ◽  
Author(s):  
Vinod K. Batra ◽  
William A. Beard ◽  
David D. Shock ◽  
Lars C. Pedersen ◽  
Samuel H. Wilson
Keyword(s):  
Dna Polymerase ◽  
Active Site ◽  
Abasic Site ◽  
Dna Polymerase Β

scholarly journals Influence of DNA Structure on DNA Polymerase β Active Site Function

2004 ◽  
Vol 279 (30) ◽  
pp. 31921-31929 ◽  
Author(s):  
William A. Beard ◽  
David D. Shock ◽  
Samuel H. Wilson
Keyword(s):  
Dna Polymerase ◽  
Active Site ◽  
Dna Structure ◽  
Dna Polymerase Β ◽  
Site Function

scholarly journals Threonine 79 Is a Hinge Residue That Governs the Fidelity of DNA Polymerase β by Helping to Position the DNA within the Active Site

2002 ◽  
Vol 277 (38) ◽  
pp. 35550-35560 ◽  
Author(s):  
Mausumi Maitra ◽  
Andrew Gudzelak ◽  
Shu-Xia Li ◽  
Yoshihiro Matsumoto ◽  
Kristin A. Eckert ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Active Site ◽  
Dna Polymerase Β

scholarly journals Remote Mutations Induce Functional Changes in Active Site Residues of Human DNA Polymerase β

Biochemistry ◽  
2017 ◽  
Vol 56 (18) ◽  
pp. 2363-2371 ◽  
Author(s):  
Brian E. Eckenroth ◽  
Jamie B. Towle-Weicksel ◽  
Antonia A. Nemec ◽  
Drew L. Murphy ◽  
Joann B. Sweasy ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Active Site ◽  
Active Site Residues ◽  
Dna Polymerase Β ◽  
Functional Changes ◽  
Human Dna
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