Genomes and Genes
Summary: A purine or pyrimidine base bonded to a DEOXYRIBOSE containing a bond to a phosphate group.
- Zhang H, Cao W, Zakharova E, Konigsberg W, De La Cruz E. Fluorescence of 2-aminopurine reveals rapid conformational changes in the RB69 DNA polymerase-primer/template complexes upon binding and incorporation of matched deoxynucleoside triphosphates. Nucleic Acids Res. 2007;35:6052-62 pubmed
- DeLucia A, Grindley N, Joyce C. Conformational changes during normal and error-prone incorporation of nucleotides by a Y-family DNA polymerase detected by 2-aminopurine fluorescence. Biochemistry. 2007;46:10790-803 pubmed
- Zhang L, Rechkoblit O, Wang L, Patel D, Shapiro R, Broyde S. Mutagenic nucleotide incorporation and hindered translocation by a food carcinogen C8-dG adduct in Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4): modeling and dynamics studies. Nucleic Acids Res. 2006;34:3326-37 pubmed..2006), PLoS Biol., 4, e11). However, N2-dG adducts, which can reside on the minor groove side, appear to cause less hindrance when in this position...
- Xu H, Faber C, Uchiki T, Fairman J, Racca J, Dealwis C. Structures of eukaryotic ribonucleotide reductase I provide insights into dNTP regulation. Proc Natl Acad Sci U S A. 2006;103:4022-7 pubmed..Finally, the substrate ribose binds with its 3' hydroxyl closer than its 2' hydroxyl to C218 of the catalytic redox pair. We also see a conserved water molecule at the catalytic site in all our structures, near the ribose 2' hydroxyl. ..
- Mauger F, Jaunay O, Chamblain V, Reichert F, Bauer K, Gut I, et al. SNP genotyping using alkali cleavage of RNA/DNA chimeras and MALDI time-of-flight mass spectrometry. Nucleic Acids Res. 2006;34:e18 pubmed
- Song S, Pursell Z, Copeland W, Longley M, Kunkel T, Mathews C. DNA precursor asymmetries in mammalian tissue mitochondria and possible contribution to mutagenesis through reduced replication fidelity. Proc Natl Acad Sci U S A. 2005;102:4990-5 pubmed
- Nick McElhinny S, Ramsden D. Polymerase mu is a DNA-directed DNA/RNA polymerase. Mol Cell Biol. 2003;23:2309-15 pubmed
- Roig V, Asseline U. Oligo-2'-deoxyribonucleotides containing uracil modified at the 5-position with linkers ending with guanidinium groups. J Am Chem Soc. 2003;125:4416-7 pubmedWe report here the synthesis and binding studies of oligo-2'-deoxyribonucleotides (ODNs) containing 2'-deoxyuridines, modified at the 5-position by linkers ending with either one or two guanidinium groups...
- Diamond T, Roshal M, Jamburuthugoda V, Reynolds H, Merriam A, Lee K, et al. Macrophage tropism of HIV-1 depends on efficient cellular dNTP utilization by reverse transcriptase. J Biol Chem. 2004;279:51545-53 pubmed
- Pontarin G, Ferraro P, Håkansson P, Thelander L, Reichard P, Bianchi V. p53R2-dependent ribonucleotide reduction provides deoxyribonucleotides in quiescent human fibroblasts in the absence of induced DNA damage. J Biol Chem. 2007;282:16820-8 pubmed..Total ribonucleotide reduction in quiescent cells amounted to only 2-3% of cycling cells. We suggest that in quiescent cells an important function of p53R2 is to provide deoxynucleotides for mitochondrial DNA replication. ..
- Van Cor Hosmer S, Daddacha W, Kim B. Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Virology. 2010;406:253-60 pubmed publisher..These data support a mechanistic interaction between cPPT and M184I RT with respect to viral replication and sensitivity to 3TC. ..
- Purohit V, Grindley N, Joyce C. Use of 2-aminopurine fluorescence to examine conformational changes during nucleotide incorporation by DNA polymerase I (Klenow fragment). Biochemistry. 2003;42:10200-11 pubmed
- Song S, Wheeler L, Mathews C. Deoxyribonucleotide pool imbalance stimulates deletions in HeLa cell mitochondrial DNA. J Biol Chem. 2003;278:43893-6 pubmed..Our finding of dTTP and dGTP elevations and dATP depletion in mitochondrial dNTP pools are consistent with a mutagenic mechanism involving T-G mispairing followed by a next-nucleotide effect involving T insertion opposite A...
- Harris V, Smith C, Jonathan Cummins W, Hamilton A, Adams H, Dickman M, et al. The effect of tautomeric constant on the specificity of nucleotide incorporation during DNA replication: support for the rare tautomer hypothesis of substitution mutagenesis. J Mol Biol. 2003;326:1389-401 pubmed..Furthermore, they imply that DNA polymerases impose specific steric requirements on the base-pair during nucleotide incorporation. ..
- DeLucia A, Chaudhuri S, Potapova O, Grindley N, Joyce C. The properties of steric gate mutants reveal different constraints within the active sites of Y-family and A-family DNA polymerases. J Biol Chem. 2006;281:27286-91 pubmed..In Klenow fragment the templating base is more rigidly held, so that changes in base pair geometry would affect the dNTP position, allowing the Glu710 side chain to serve as a sensor of nascent mispairs. ..
- Batiuk T, Schnizlein Bick C, Plotkin Z, Dagher P. Guanine nucleosides and Jurkat cell death: roles of ATP depletion and accumulation of deoxyribonucleotides. Am J Physiol Cell Physiol. 2001;281:C1776-84 pubmed..In conclusion, guanosine and deoxyguanosine are toxic to Jurkat cells through two mechanisms: ATP depletion, causing necrosis, and the accumulation of dGTP, resulting in apoptosis. ..
- Xia S, Eom S, Konigsberg W, Wang J. Bidentate and tridentate metal-ion coordination states within ternary complexes of RB69 DNA polymerase. Protein Sci. 2012;21:447-51 pubmed publisher..88 Å resolution. Our observations suggest that several distinct metal-ion coordination states can exist at the ground state in the polymerase active site and that base selectivity is unlikely to be based on metal-ion coordination alone. ..
- Ashley N, Adams S, Slama A, Zeviani M, Suomalainen A, Andreu A, et al. Defects in maintenance of mitochondrial DNA are associated with intramitochondrial nucleotide imbalances. Hum Mol Genet. 2007;16:1400-11 pubmed..Because deviations from the normal concentrations of dNTPs are known to be mutagenic, we suggest that intramitochondrial nucleotide imbalance could underlie the multiple mtDNA mutations observed in these patients. ..
- Jamburuthugoda V, Santos Velazquez J, Skasko M, Operario D, Purohit V, Chugh P, et al. Reduced dNTP binding affinity of 3TC-resistant M184I HIV-1 reverse transcriptase variants responsible for viral infection failure in macrophage. J Biol Chem. 2008;283:9206-16 pubmed publisher..This can restrict ground state dNTP binding and lead to inefficient DNA synthesis particularly at low dNTP concentrations, ultimately contributing to viral replication failure in macrophage and instability in vivo of the M184I mutation. ..
- Tasara T, Angerer B, Damond M, Winter H, Dörhöfer S, Hubscher U, et al. Incorporation of reporter molecule-labeled nucleotides by DNA polymerases. II. High-density labeling of natural DNA. Nucleic Acids Res. 2003;31:2636-46 pubmed..Moreover, we present systematic testing of various combinations of fluorescent dye-modified dNTPs enabling the simultaneous labeling of DNA with up to four differently modified dNTPs. ..
- Giller G, Tasara T, Angerer B, Mühlegger K, Amacker M, Winter H. Incorporation of reporter molecule-labeled nucleotides by DNA polymerases. I. Chemical synthesis of various reporter group-labeled 2'-deoxyribonucleoside-5'-triphosphates. Nucleic Acids Res. 2003;31:2630-5 pubmed..Our data suggest that the incorporation efficiency depends on the selected dye, the nucleobase or a combination of both. ..
- Pontarin G, Ferraro P, Rampazzo C, Kollberg G, Holme E, Reichard P, et al. Deoxyribonucleotide metabolism in cycling and resting human fibroblasts with a missense mutation in p53R2, a subunit of ribonucleotide reductase. J Biol Chem. 2011;286:11132-40 pubmed publisher..We speculate that this compensatory mechanism suffices to maintain mtDNA in fibroblasts but not in muscle cells with a larger content of mtDNA necessary for their high energy requirements. ..
- Bakhtina M, Lee S, Wang Y, Dunlap C, Lamarche B, Tsai M. Use of viscogens, dNTPalphaS, and rhodium(III) as probes in stopped-flow experiments to obtain new evidence for the mechanism of catalysis by DNA polymerase beta. Biochemistry. 2005;44:5177-87 pubmed..The methodologies can be used to examine other DNA polymerases to answer whether the properties of Pol beta are exceptional or general...
- Håkansson P, Hofer A, Thelander L. Regulation of mammalian ribonucleotide reduction and dNTP pools after DNA damage and in resting cells. J Biol Chem. 2006;281:7834-41 pubmed
- Hays H, Berdis A. Manganese substantially alters the dynamics of translesion DNA synthesis. Biochemistry. 2002;41:4771-8 pubmed..Various models are discussed in an attempt to explain the effect of metal ion substitution on the dynamics of translesion DNA replication. ..
- Jia L, Geacintov N, Broyde S. The N-clasp of human DNA polymerase kappa promotes blockage or error-free bypass of adenine- or guanine-benzo[a]pyrenyl lesions. Nucleic Acids Res. 2008;36:6571-84 pubmed publisher..Absence of the N-clasp in Dpo4 explains the error-prone processing of the same lesion by this enzyme. Thus, our studies elucidate structure-function relationships in the fidelity of lesion bypass. ..
- Akman H, Dorado B, Lopez L, García Cazorla A, Vila M, Tanabe L, et al. Thymidine kinase 2 (H126N) knockin mice show the essential role of balanced deoxynucleotide pools for mitochondrial DNA maintenance. Hum Mol Genet. 2008;17:2433-40 pubmed publisher..The H126N TK2 mouse is the first knock-in animal model of human MDS and demonstrates that the severity of TK2 deficiency in tissues may determine the organ-specific phenotype. ..
- Washington M, Johnson R, Prakash L, Prakash S. Human DNA polymerase iota utilizes different nucleotide incorporation mechanisms dependent upon the template base. Mol Cell Biol. 2004;24:936-43 pubmed
- Kumar D, Abdulovic A, Viberg J, Nilsson A, Kunkel T, Chabes A. Mechanisms of mutagenesis in vivo due to imbalanced dNTP pools. Nucleic Acids Res. 2011;39:1360-71 pubmed publisher..An interesting mutational strand bias is observed in one rnr1 strain, suggesting that the S-phase checkpoint selectively prevents replication errors during leading strand replication. ..
- Howell C, Prakash S, Washington M. Pre-steady-state kinetic studies of protein-template-directed nucleotide incorporation by the yeast Rev1 protein. Biochemistry. 2007;46:13451-9 pubmed..Moreover, on the basis of these findings and on structures of the unrelated Escherichia coli MutM DNA glycosylase, we suggest the possible structures for the ternary complexes of Rev1p with the other incoming dNTPs. ..
- Zhou G, Kamahori M, Okano K, Harada K, Kambara H. Miniaturized pyrosequencer for DNA analysis with capillaries to deliver deoxynucleotides. Electrophoresis. 2001;22:3497-504 pubmed..The new system is successfully applied to sequence a GC rich region or a region close to a priming region where misreading frequently occurs. A rapid analysis for a short DNA was easily achieved with this small instrument. ..
- Shah A, Maitra M, Sweasy J. Variants of DNA polymerase Beta extend mispaired DNA due to increased affinity for nucleotide substrate. Biochemistry. 2003;42:10709-17 pubmed
- Devadoss B, Lee I, Berdis A. Is a thymine dimer replicated via a transient abasic site intermediate? A comparative study using non-natural nucleotides. Biochemistry. 2007;46:4486-98 pubmed..The data for both nucleotide incorporation and excision are used to propose models accounting for polymerase "switching" during translesion DNA synthesis. ..
- Desler C, Munch Petersen B, Stevnsner T, Matsui S, Kulawiec M, Singh K, et al. Mitochondria as determinant of nucleotide pools and chromosomal stability. Mutat Res. 2007;625:112-24 pubmed..Our results suggest that mitochondria are central players in maintaining genomic stability and in controlling essential nuclear processes such as upholding a balanced supply of nucleotides. ..
- Zhang X, Lee I, Berdis A. Evaluating the contributions of desolvation and base-stacking during translesion DNA synthesis. Org Biomol Chem. 2004;2:1703-11 pubmed..This result indicates that indolyl-2'-deoxyriboside triphosphate acts as an indiscriminate chain terminator of DNA synthesis that may have unique therapeutic applications. ..
- Chiaramonte M, Moore C, Kincaid K, Kuchta R. Facile polymerization of dNTPs bearing unnatural base analogues by DNA polymerase alpha and Klenow fragment (DNA polymerase I). Biochemistry. 2003;42:10472-81 pubmed..The implications of these results with respect to how polymerases discriminate between correct and incorrect dNTPs are discussed. ..
- Ferraro P, Franzolin E, Pontarin G, Reichard P, Bianchi V. Quantitation of cellular deoxynucleoside triphosphates. Nucleic Acids Res. 2010;38:e85 pubmed publisher..We suggest that in some earlier reports ribonucleotide incorporation may have caused too high values for dGTP and dCTP. ..
- Minnick D, Liu L, Grindley N, Kunkel T, Joyce C. Discrimination against purine-pyrimidine mispairs in the polymerase active site of DNA polymerase I: a structural explanation. Proc Natl Acad Sci U S A. 2002;99:1194-9 pubmed..Moreover, this same side chain enhances the stability of incoming correct dNTPs, such that loss of this interaction on removal of the side chain leads to lower selectivity against mismatches involving incoming pyrimidines. ..
- Ruiz J, Juarez R, Garcia Diaz M, Terrados G, Picher A, González Barrera S, et al. Lack of sugar discrimination by human Pol mu requires a single glycine residue. Nucleic Acids Res. 2003;31:4441-9 pubmed..The unusual capacity to insert both rNTPs and dNTPs will be discussed in the context of the predicted roles of Pol mu in DNA repair. ..
- Kumar S, Lamarche B, Tsai M. Use of damaged DNA and dNTP substrates by the error-prone DNA polymerase X from African swine fever virus. Biochemistry. 2007;46:3814-25 pubmed..Our findings are discussed in light of ASFV biology and the mutagenic DNA repair hypothesis described above. ..
- Gaglio D, Soldati C, Vanoni M, Alberghina L, Chiaradonna F. Glutamine deprivation induces abortive s-phase rescued by deoxyribonucleotides in k-ras transformed fibroblasts. PLoS ONE. 2009;4:e4715 pubmed publisher..transformed cells as well as the ability to execute the G(1) to S transition is restored by adding the four deoxyribonucleotides, indicating that the arrest of proliferation of K-ras transformed cells induced by glutamine depletion is ..
- DeLucia A, Grindley N, Joyce C. An error-prone family Y DNA polymerase (DinB homolog from Sulfolobus solfataricus) uses a 'steric gate' residue for discrimination against ribonucleotides. Nucleic Acids Res. 2003;31:4129-37 pubmed..When making a deletion error, ribonucleotide discrimination by wild-type and F12A Dbh is the same as in normal DNA synthesis, indicating that the geometry of nucleotide binding is similar in both circumstances. ..
- Sabouri N, Viberg J, Goyal D, Johansson E, Chabes A. Evidence for lesion bypass by yeast replicative DNA polymerases during DNA damage. Nucleic Acids Res. 2008;36:5660-7 pubmed publisherThe enzyme ribonucleotide reductase, responsible for the synthesis of deoxyribonucleotides (dNTP), is upregulated in response to DNA damage in all organisms...
- Ferraro P, Pontarin G, Crocco L, Fabris S, Reichard P, Bianchi V. Mitochondrial deoxynucleotide pools in quiescent fibroblasts: a possible model for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). J Biol Chem. 2005;280:24472-80 pubmed..Other dNTPs are marginally affected. Deoxyuridine does not increase the normal dNTP pools but gives rise to a small dUTP and a large dUMP pool, both turning over rapidly. We discuss these results in relation to MNGIE...
- Ruparel H, Bi L, Li Z, Bai X, Kim D, Turro N, et al. Design and synthesis of a 3'-O-allyl photocleavable fluorescent nucleotide as a reversible terminator for DNA sequencing by synthesis. Proc Natl Acad Sci U S A. 2005;102:5932-7 pubmed
- Yasui M, Dong H, Bonala R, Suzuki N, Ohmori H, Hanaoka F, et al. Mutagenic properties of 3-(deoxyguanosin-N2-yl)-2-acetylaminofluorene, a persistent acetylaminofluorene-derived DNA adduct in mammalian cells. Biochemistry. 2004;43:15005-13 pubmed
- Alexandre J, Roy B, Topalis D, Pochet S, Perigaud C, Deville Bonne D. Enantioselectivity of human AMP, dTMP and UMP-CMP kinases. Nucleic Acids Res. 2007;35:4895-904 pubmed..This in vitro information was then used to develop the in vivo activation pathway for L-dT. ..
- Topalis D, Collinet B, Gasse C, Dugue L, Balzarini J, Pochet S, et al. Substrate specificity of vaccinia virus thymidylate kinase. FEBS J. 2005;272:6254-65 pubmed..Several thymidine and dTMP derivatives were found to bind the enzyme with micromolar affinities. The present study provides the basis for the design of specific inhibitors or substrates for poxvirus TMP kinase. ..