Stability and Polymerase Recognition of Pyridine Nucleobase Analogues: Role of Minor-Groove H-Bond Acceptors

2006 ◽  
Vol 118 (46) ◽  
pp. 7973-7976 ◽  
Author(s):  
Yoonkyung Kim ◽  
Aaron M. Leconte ◽  
Yoshiyuki Hari ◽  
Floyd E. Romesberg
Keyword(s):  
PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e69933 ◽  
Author(s):  
Deepak K. Jangir ◽  
Suman Kundu ◽  
Ranjana Mehrotra
Keyword(s):  

Author(s):  
Paola Monti ◽  
Giorgia Foggetti ◽  
Paola Menichini ◽  
Alberto Inga ◽  
Barry Gold ◽  
...  

2004 ◽  
Vol 126 (36) ◽  
pp. 11338-11349 ◽  
Author(s):  
Nahoum G. Anthony ◽  
Blair F. Johnston ◽  
Abedawn I. Khalaf ◽  
Simon P. MacKay ◽  
John A. Parkinson ◽  
...  

2020 ◽  
Vol 48 (20) ◽  
pp. 11322-11334
Author(s):  
Tomáš Bouchal ◽  
Ivo Durník ◽  
Viktor Illík ◽  
Kamila Réblová ◽  
Petr Kulhánek

Abstract Mismatch repair is a highly conserved cellular pathway responsible for repairing mismatched dsDNA. Errors are detected by the MutS enzyme, which most likely senses altered mechanical property of damaged dsDNA rather than a specific molecular pattern. While the curved shape of dsDNA in crystallographic MutS/DNA structures suggests the role of DNA bending, the theoretical support is not fully convincing. Here, we present a computational study focused on a base-pair opening into the minor groove, a specific base-pair motion observed upon interaction with MutS. Propensities for the opening were evaluated in terms of two base-pair parameters: Opening and Shear. We tested all possible base pairs in anti/anti, anti/syn and syn/anti orientations and found clear discrimination between mismatches and canonical base-pairs only for the opening into the minor groove. Besides, the discrimination gap was also confirmed in hotspot and coldspot sequences, indicating that the opening could play a more significant role in the mismatch recognition than previously recognized. Our findings can be helpful for a better understanding of sequence-dependent mutability. Further, detailed structural characterization of mismatches can serve for designing anti-cancer drugs targeting mismatched base pairs.


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.


Biochemistry ◽  
2014 ◽  
Vol 53 (35) ◽  
pp. 5601-5612 ◽  
Author(s):  
Xiaoqian Xu ◽  
Akli Ben Imeddourene ◽  
Loussiné Zargarian ◽  
Nicolas Foloppe ◽  
Olivier Mauffret ◽  
...  

2012 ◽  
Vol 56 ◽  
pp. 39-47 ◽  
Author(s):  
Abedawn I. Khalaf ◽  
Claire Bourdin ◽  
David Breen ◽  
Gavin Donoghue ◽  
Fraser J. Scott ◽  
...  

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