Short Lexitropsin that Recognizes the DNA Minor Groove at 5‘-ACTAGT-3‘:  Understanding the Role of Isopropyl-thiazole

2004 ◽  
Vol 126 (36) ◽  
pp. 11338-11349 ◽  
Author(s):  
Nahoum G. Anthony ◽  
Blair F. Johnston ◽  
Abedawn I. Khalaf ◽  
Simon P. MacKay ◽  
John A. Parkinson ◽  
...  
2004 ◽  
Vol 24 (16) ◽  
pp. 6900-6906 ◽  
Author(s):  
M. Todd Washington ◽  
Irina G. Minko ◽  
Robert E. Johnson ◽  
Lajos Haracska ◽  
Thomas M. Harris ◽  
...  

ABSTRACT Rev1, a member of the Y family of DNA polymerases, functions in lesion bypass together with DNA polymerase ζ (Polζ). Rev1 is a highly specialized enzyme in that it incorporates only a C opposite template G. While Rev1 plays an indispensable structural role in Polζ-dependent lesion bypass, the role of its DNA synthetic activity in lesion bypass has remained unclear. Since interactions of DNA polymerases with the DNA minor groove contribute to the nearly equivalent efficiencies and fidelities of nucleotide incorporation opposite each of the four template bases, here we examine the possibility that unlike other DNA polymerases, Rev1 does not come into close contact with the minor groove of the incipient base pair, and that enables it to incorporate a C opposite the N 2-adducted guanines in DNA. To test this idea, we examined whether Rev1 could incorporate a C opposite the γ-hydroxy-1,N 2-propano-2′deoxyguanosine DNA minor-groove adduct, which is formed from the reaction of acrolein with the N 2 of guanine. Acrolein, an α,β-unsaturated aldehyde, is generated in vivo as the end product of lipid peroxidation and from other oxidation reactions. We show here that Rev1 efficiently incorporates a C opposite this adduct from which Polζ subsequently extends, thereby completing the lesion bypass reaction. Based upon these observations, we suggest that an important role of the Rev1 DNA synthetic activity in lesion bypass is to incorporate a C opposite the various N 2-guanine DNA minor-groove adducts that form in DNA.


2004 ◽  
Vol 24 (13) ◽  
pp. 5687-5693 ◽  
Author(s):  
M. Todd Washington ◽  
Irina G. Minko ◽  
Robert E. Johnson ◽  
William T. Wolfle ◽  
Thomas M. Harris ◽  
...  

ABSTRACT DNA polymerase ι (Polι) is a member of the Y family of DNA polymerases, which promote replication through DNA lesions. The role of Polι in lesion bypass, however, has remained unclear. Polι is highly unusual in that it incorporates nucleotides opposite different template bases with very different efficiencies and fidelities. Since interactions of DNA polymerases with the DNA minor groove provide for the nearly equivalent efficiencies and fidelities of nucleotide incorporation opposite each of the four template bases, we considered the possibility that Polι differs from other DNA polymerases in not being as sensitive to distortions of the minor groove at the site of the incipient base pair and that this enables it to incorporate nucleotides opposite highly distorting minor-groove DNA adducts. To check the validity of this idea, we examined whether Polι could incorporate nucleotides opposite the γ-HOPdG adduct, which is formed from an initial reaction of acrolein with the N2 of guanine. We show here that Polι incorporates a C opposite this adduct with nearly the same efficiency as it does opposite a nonadducted template G residue. The subsequent extension step, however, is performed by Polκ, which efficiently extends from the C incorporated opposite the adduct. Based upon these observations, we suggest that an important biological role of Polι and Polκ is to act sequentially to carry out the efficient and accurate bypass of highly distorting minor-groove DNA adducts of the purine bases.


1989 ◽  
Vol 217 (2) ◽  
pp. 163-172 ◽  
Author(s):  
Paul J. Smith ◽  
Paul G. Debenham ◽  
James V. Watson

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e69933 ◽  
Author(s):  
Deepak K. Jangir ◽  
Suman Kundu ◽  
Ranjana Mehrotra
Keyword(s):  

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