English Journal

Is the DPT tautomerization of the long A·G Watson-Crick DNA base mispair a source of the adenine and guanine mutagenic tautomers? A QM and QTAIM response to the biologically important question.

Brovarets' OO1, Zhurakivsky RO, Hovorun DM.Author information 1Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150 Akademika Zabolotnoho Str., 03680, Kyiv, Ukraine ; Research and Educational Center "State Key Laboratory of Molecular and Cell Biology", 150 Akademika Zabolotnoho Str., 03680, Kyiv, Ukraine; Department of Molecular Biology, Biotechnology and Biophysics, Institute of High Technologies, Taras Shevchenko National University of Kyiv, 2-h Akademika Hlushkova Ave., 03022, Kyiv, Ukraine.AbstractHerein, we first address the question posed in the title by establishing the tautomerization trajectory via the double proton transfer of the adenine·guanine (A·G) DNA base mispair formed by the canonical tautomers of the A and G bases into the A*·G* DNA base mispair, involving mutagenic tautomers, with the use of the quantum-mechanical calculations and quantum theory of atoms in molecules (QTAIM). It was detected that the A·G ↔ A*·G* tautomerization proceeds through the asynchronous concerted mechanism. It was revealed that the A·G base mispair is stabilized by the N6H···O6 (5.68) and N1H···N1 (6.51) hydrogen bonds (H-bonds) and the N2H···HC2 dihydrogen bond (DH-bond) (0.68 kcal·mol(-1) ), whereas the A*·G* base mispair-by the O6H···N6 (10.88), N1H···N1 (7.01) and C2H···N2 H-bonds (0.42 kcal·mol(-1) ). The N2H···HC2 DH-bond smoothly and without bifurcation transforms into the C2H···N2 H-bond at the IRC = -10.07 Bohr in the course of the A·G ↔ A*·G* tautomerization. Using the sweeps of the energies of the intermolecular H-bonds, it was observed that the N6H···O6 H-bond is anticooperative to the two others-N1H···N1 and N2H···HC2 in the A·G base mispair, while the latters are significantly cooperative, mutually strengthening each other. In opposite, all three O6H···N6, N1H···N1, and C2H···N2 H-bonds are cooperative in the A*·G* base mispair. All in all, we established the dynamical instability of the А*·G* base mispair with a short lifetime (4.83·10(-14) s), enabling it not to be deemed feasible source of the A* and G* mutagenic tautomers of the DNA bases. The small lifetime of the А*·G* base mispair is predetermined by the negative value of the Gibbs free energy for the A*·G* → A·G transition. Moreover, all of the six low-frequency intermolecular vibrations cannot develop during this lifetime that additionally confirms the aforementioned results. Thus, the A*·G* base mispair cannot be considered as a source of the mutagenic tautomers of the DNA bases, as the A·G base mispair dissociates during DNA replication exceptionally into the A and G monomers in the canonical tautomeric form. © 2013 Wiley Periodicals, Inc.
Journal of computational chemistry.J Comput Chem.2014 Mar 5;35(6):451-66. doi: 10.1002/jcc.23515. Epub 2013 Dec 30.
Herein, we first address the question posed in the title by establishing the tautomerization trajectory via the double proton transfer of the adenine·guanine (A·G) DNA base mispair formed by the canonical tautomers of the A and G bases into the A*·G* DNA base mispair, involving mutagenic tautomer
PMID 24382756

Mispair-specific recruitment of Mlh1-Pms1 identifies repair substrates of Saccharomyces cerevisiae Msh2-Msh3.

Srivatsan A1, Bowen N, Kolodner RD.Author information 1Ludwig Institute for Cancer Research, United States.AbstractDNA mismatch repair (MMR)a is initiated by either the Msh2-Msh6 or the Msh2-Msh3 mispair recognition heterodimer. Here, we optimized the expression and purification of Saccharomyces cerevisiae Msh2-Msh3 and performed a comparative study of Msh2-Msh3 and Msh2-Msh6 for mispair binding, sliding clamp formation and Mlh1-Pms1 recruitment. Msh2-Msh3 formed sliding clamps and recruited Mlh1-Pms1 on +1, +2, +3 and +4 insertion/deletions and CC, AA and possibly GG mispairs whereas Msh2-Msh6 formed mispair-dependent sliding clamps and recruited Mlh1-Pms1 on 7 of the 8 possible base:base mispairs, the +1 insertion/deletion mispair and to a low level on the +2 but not the +3 or +4 insertion/deletion mispairs and not on the CC mispair. The mispair specificity of sliding clamp formation and Mlh1-Pms1 recruitment but not mispair binding alone correlated best with genetic data on the mispair specificity of Msh2-Msh3- and Msh2-Msh6-dependent MMR in vivo. Analysis of an Msh2-Msh6/Msh3 chimeric protein and mutant Msh2-Msh3 complexes showed that the nucleotide binding domain and communicating regions but not the mispair binding domain of Msh2-Msh3 are responsible for the extremely rapid dissociation of Msh2-Msh3 sliding clamps from DNA relative to that seen for Msh2-Msh6 and that amino acid residues predicted to stabilize Msh2-Msh3 interactions with bent, strand separated mispair-containing DNA are more critical for the recognition of small +1 insertion/deletions than larger +4 insertion/deletions.
The Journal of biological chemistry.J Biol Chem.2014 Feb 18. [Epub ahead of print]
DNA mismatch repair (MMR)a is initiated by either the Msh2-Msh6 or the Msh2-Msh3 mispair recognition heterodimer. Here, we optimized the expression and purification of Saccharomyces cerevisiae Msh2-Msh3 and performed a comparative study of Msh2-Msh3 and Msh2-Msh6 for mispair binding, sliding clamp f
PMID 24550389

Fidelity of nick sealing by Deinococcus radiodurans RNA ligase: effects of 3' -OH and 5' -PO4 base mispairs and damaged base lesions.

Schmier BJ1, Shuman S.Author information 1Molecular Biology Program, Sloan-Kettering Institute, New York, NY 10065.AbstractDeinococcus radiodurans RNA ligase (DraRnl) is the founding member of a family of end-joining enzymes encoded by diverse microbes and viruses. DraRnl ligates 3' -OH, 5' -PO4 nicks in double-stranded nucleic acids in which the nick 3' -OH end is RNA. Here we gauge effects of 3' -OH and 5' -PO4 base mispairs and damaged base lesions on the rate of nick sealing. DraRnl is indifferent to identity of the 3' -OH nucleobase, provided it is correctly paired. With 3' -OH mispairs, DraRnl sealing rate varies widely, with G:T and A:C mispairs being the best substrates and G:G, G:A and A:A mispairs being the worst. DraRnl accepts 3' A:oxoG as correctly paired, while discriminating against U:oxoG and G:oxoG mispairs. DraRnl displays high activity and low fidelity in sealing 3' -OH ends opposite an oxoA lesion. It prefers 3' -OH adenosine when sealing opposite an abasic template site. With 5' -PO4 mispairs, DraRnl seals a 5' T:G mispair as well as it does a 5' C:G pair; in most other respects, ligation fidelity at 5' mispairs is similar to 3' mispairs. DraRnl accepts a 5' A:oxoG end as correctly paired, yet is more tolerant of 5' T:oxoG and 5' G:oxoG mispairs than the equivalent configurations on the 3' side of the nick. At 5' N:abasic nicks, DraRnl prefers to ligate when the N base is a purine. The biochemical properties of DraRnl are compatible with its participation in the templated repair of RNA damage or in the sealing of filled DNA gaps that have a 3' "ribo-patch".
Journal of bacteriology.J Bacteriol.2014 Feb 14. [Epub ahead of print]
Deinococcus radiodurans RNA ligase (DraRnl) is the founding member of a family of end-joining enzymes encoded by diverse microbes and viruses. DraRnl ligates 3' -OH, 5' -PO4 nicks in double-stranded nucleic acids in which the nick 3' -OH end is RNA. Here we gauge effects of 3' -OH and 5' -PO4 base m
PMID 24532777

Japanese Journal

GC→CGトランスバージョンを抑制するMutYタンパクの機能

張秋梅,橋本清弘,米井脩治
日本分子生物学会年会プログラム・講演要旨集 21, 187, 1998-12-01
NAID 10002855015

Escherichia coli MutY protein has a guanine-DNA glycosylase that acts on 7,8-dihydro-8-oxoguanine : guanine mispair to prevent spontaneous GC-CG transversions