scholarly journals An Incoming Nucleotide Imposes an anti to syn Conformational Change on the Templating Purine in the Human DNA Polymerase-ι Active Site

Structure ◽  
2006 ◽  
Vol 14 (4) ◽  
pp. 749-755 ◽  
Author(s):  
Deepak T. Nair ◽  
Robert E. Johnson ◽  
Louise Prakash ◽  
Satya Prakash ◽  
Aneel K. Aggarwal
Keyword(s):  
Conformational Change ◽  
Dna Polymerase ◽  
Active Site ◽  
Human Dna ◽  
Dna Polymerase Ι

scholarly journals Role of Hoogsteen Edge Hydrogen Bonding at Template Purines in Nucleotide Incorporation by Human DNA Polymerase ι

2006 ◽  
Vol 26 (17) ◽  
pp. 6435-6441 ◽  
Author(s):  
Robert E. Johnson ◽  
Lajos Haracska ◽  
Louise Prakash ◽  
Satya Prakash
Keyword(s):  
Hydrogen Bonding ◽  
Dna Polymerase ◽  
Active Site ◽  
Dna Polymerases ◽  
Human Dna ◽  
Nucleotide Incorporation ◽  
Template Specificity ◽  
Hydrogen Bonding Potential ◽  
Dna Polymerase Ι

ABSTRACT Human DNA polymerase ι (Pol ι) differs from other DNA polymerases in that it exhibits a marked template specificity, being more efficient and accurate opposite template purines than opposite pyrimidines. The crystal structures of Pol ι with template A and incoming dTTP and with template G and incoming dCTP have revealed that in the Pol ι active site, the templating purine adopts a syn conformation and forms a Hoogsteen base pair with the incoming pyrimidine which remains in the anti conformation. By using 2-aminopurine and purine as the templating residues, which retain the normal N7 position but lack the N6 of an A or the O6 of a G, here we provide evidence that whereas hydrogen bonding at N6 is dispensable for the proficient incorporation of a T opposite template A, hydrogen bonding at O6 is a prerequisite for C incorporation opposite template G. To further analyze the contributions of O6 and N7 hydrogen bonding to DNA synthesis by Pol ι, we have examined its proficiency for replicating through the 6 O-methyl guanine and 8-oxoguanine lesions, which affect the O6 and N7 positions of template G, respectively. We conclude from these studies that for proficient T incorporation opposite template A, only the N7 hydrogen bonding is required, but for proficient C incorporation opposite template G, hydrogen bonding at both the N7 and O6 is an imperative. The dispensability of N6 hydrogen bonding for proficient T incorporation opposite template A has important biological implications, as that would endow Pol ι with the ability to replicate through lesions which impair the Watson-Crick hydrogen bonding potential at both the N1 and N6 positions of templating A.

scholarly journals Localization of the Deoxyribose Phosphate Lyase Active Site in Human DNA Polymerase ι by Controlled Proteolysis

2003 ◽  
Vol 278 (32) ◽  
pp. 29649-29654 ◽  
Author(s):  
Rajendra Prasad ◽  
Katarzyna Bebenek ◽  
Esther Hou ◽  
David D. Shock ◽  
William A. Beard ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Active Site ◽  
Human Dna ◽  
Dna Polymerase Ι

scholarly journals Human DNA Polymerase ι Incorporates dCTP Opposite Template G via a G.C+ Hoogsteen Base Pair

Structure ◽  
2005 ◽  
Vol 13 (10) ◽  
pp. 1569-1577 ◽  
Author(s):  
Deepak T. Nair ◽  
Robert E. Johnson ◽  
Louise Prakash ◽  
Satya Prakash ◽  
Aneel K. Aggarwal
Keyword(s):  
Dna Polymerase ◽  
Base Pair ◽  
Human Dna ◽  
Dna Polymerase Ι

Response of human DNA polymerase ι promoter to N-methyl-N′-nitro-N-nitrosoguanidine

2010 ◽  
Vol 29 (1) ◽  
pp. 79-86 ◽  
Author(s):  
Huifang Zhu ◽  
Yanfeng Fan ◽  
Hongjuan Jiang ◽  
Jing Shen ◽  
Hongyan Qi ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Human Dna ◽  
Dna Polymerase Ι

Replication by human DNA polymerase-ι occurs by Hoogsteen base-pairing

Nature ◽  
2004 ◽  
Vol 430 (6997) ◽  
pp. 377-380 ◽  
Author(s):  
Deepak T. Nair ◽  
Robert E. Johnson ◽  
Satya Prakash ◽  
Louise Prakash ◽  
Aneel K. Aggarwal
Keyword(s):  
Dna Polymerase ◽  
Base Pairing ◽  
Human Dna ◽  
Hoogsteen Base Pairing ◽  
Dna Polymerase Ι

scholarly journals Human DNA Polymerase ι Promotes Replication through a Ring-Closed Minor-Groove Adduct That Adopts a syn Conformation in DNA

2005 ◽  
Vol 25 (19) ◽  
pp. 8748-8754 ◽  
Author(s):  
William T. Wolfle ◽  
Robert E. Johnson ◽  
Irina G. Minko ◽  
R. Stephen Lloyd ◽  
Satya Prakash ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Dna Polymerases ◽  
Minor Groove ◽  
Dna Lesions ◽  
Unsaturated Aldehyde ◽  
Cyclic Form ◽  
Human Dna ◽  
A Minor ◽  
Dna Polymerase Ι

ABSTRACT Acrolein, an α,β-unsaturated aldehyde, is generated in vivo as the end product of lipid peroxidation and from oxidation of polyamines. The reaction of acrolein with the N 2 group of guanine in DNA leads to the formation of a cyclic adduct, γ-hydroxy-1,N 2-propano-2′-deoxyguanosine (γ-HOPdG). Previously, we have shown that proficient replication through the γ-HOPdG adduct can be mediated by the sequential action of human DNA polymerases (Pols) ι and κ, in which Polι incorporates either pyrimidine opposite γ-HOPdG, but Polκ extends only from the cytosine. Since γ-HOPdG can adopt either a ring-closed cyclic form or a ring-opened form in DNA, to better understand the mechanisms that Pols ι and κ employ to promote replication through this lesion, we have examined the ability of these polymerases to replicate through the structural analogs of γ-HOPdG that are permanently either ring closed or ring opened. Our studies with these model adducts show that whereas the ring-opened form of γ-HOPdG is not inhibitory to synthesis by human Pols η, ι, or κ, only Polι is able to incorporate nucleotides opposite the ring-closed form, which is known to adopt a syn conformation in DNA. From these studies, we infer that (i) Pols η, ι, and κ have the ability to proficiently replicate through minor-groove DNA lesions that do not perturb the Watson-Crick hydrogen bonding of the template base with the incoming nucleotide, and (ii) Polι can accommodate a minor-groove-adducted template purine which adopts a syn conformation in DNA and forms a Hoogsteen base pair with the incoming nucleotide.

Roles of the active site residues and metal cofactors in noncanonical base-pairing during catalysis by human DNA polymerase iota

DNA Repair ◽  
2014 ◽  
Vol 22 ◽  
pp. 67-76 ◽  
Author(s):  
Alena V. Makarova ◽  
Artem Ignatov ◽  
Nataliya Miropolskaya ◽  
Andrey Kulbachinskiy
Keyword(s):  
Dna Polymerase ◽  
Active Site ◽  
Active Site Residues ◽  
Base Pairing ◽  
Dna Polymerase Iota ◽  
Human Dna ◽  
Metal Cofactors
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