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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review

Base Pairing

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Disease relevance of Base Pairing


Psychiatry related information on Base Pairing

  • The e6G4-C21 base pair has a configuration similar to a normal Watson-Crick base pair, except with one three-centered hydrogen bond pair and one direct hydrogen bond between e6G4 and C21 [6].
  • A novel mutation, a C to T transition at base pair 2124 in exon 17 of the amyloid beta-protein precursor (APP) gene, has been identified by direct sequencing of amplified DNA from two Alzheimer's disease (AD) patients [7].
  • In humans, a deficiency in mitochondrial aldehyde dehydrogenase (Class 2 ALDH) activity due to a single base-pair exchange in its structural gene serves as a deterrent to excessive alcohol consumption [8].

High impact information on Base Pairing

  • Since it is now known that Watson-Crick hydrogen bonds are not necessary for efficient and selective replication of a base pair by DNA polymerase enzymes, a number of alternative physical factors have been examined to explain the efficiency of these enzymes [9].
  • Here, we report that in C. elegans, regulation by the let-7 miRNA results in degradation of its lin-41 target mRNA, despite the fact that its 3'UTR regulatory sequences can only partially base-pair with the miRNA [10].
  • Block of HAC1 mRNA translation by long-range base pairing is released by cytoplasmic splicing upon induction of the unfolded protein response [11].
  • Here we show that yeast and human POLeta replicate DNA containing 8-oxoG efficiently and accurately by inserting a cytosine across from the lesion and by proficiently extending from this base pair [12].
  • The frameshift mutation 1615delG in FANCA was compensated by two additional single base-pair deletions (1637delA and 1641delT); another FANCA frameshift mutation, 3559insG, was compensated by 3580insCGCTG; and a missense mutation in FANCC(1749T-->G, Leu496Arg) was altered by 1748C-->T, creating a cysteine codon [13].

Chemical compound and disease context of Base Pairing


Biological context of Base Pairing

  • DNA sequence analysis of three independently selected mutations revealed, in each case, a deletion of a single base pair in the cro gene [19].
  • PCR amplification of a subset of the exons, followed by electrophoresis of denatured product on native gels, identified six variant conformers specific to NF1 patients, indicating base pair changes in the gene [20].
  • Nucleotide sequence analysis demonstrates that all six mutants are single base pair alterations, occur within the leader region of the rplJ operon and are well removed from the presumed position of the primary promoter, PJ [21].
  • Here we report that three pseudogenes (U1.101, U2.13 and U3.5) are flanked by perfect short direct repeats of 16 to 19 base pairs [22].
  • Two base pair transversions (G to T, A to C) from the normal sequence predict Lys to Asn and Met to Leu amino acid substitutions at codons 670 and 671 of the APP transcript [23].

Anatomical context of Base Pairing


Associations of Base Pairing with chemical compounds

  • We propose that these molecules are intermediates in the editing process and that successive transesterifications result in the transfer of uridine residues from the gRNA 3' oligo(U) tail to an editing site, with the number of uridine residues determined by base pairing with adenine and guanine "guide" nucleotides in the gRNA [29].
  • The crystal structure of HaeIII methyltransferase convalently complexed to DNA: an extrahelical cytosine and rearranged base pairing [30].
  • We demonstrate that during the reaction many, but not all, of the adenosine residues are converted to inosine residues, and we propose that the covalent modification is responsible for the irreversible change in base pairing properties [31].
  • This 300 base pair (bp) fragment was released as naked DNA from formaldehyde-fixed, Hae III-digested minichromosomes following treatment either by pronase-SDS or by SDS alone [32].
  • A structure in which dA:dT Watson-Crick base pairs alternate with Hoogsteen syndG:dCH+ pairs appears to be the most stereochemically acceptable structure consistent with the chemical properties of this protonated DNA [33].

Gene context of Base Pairing

  • When this nucleotide is mutated to restore the consensus, base pairing with U1 snRNA is increased and the requirement for MER1 is alleviated [34].
  • The complementary DNA encoding ICAM-R is 1,781 base pairs long and the protein has five extracellular immunoglobulin-family type domains [35].
  • Analysis of the DNA cleavage patterns for dimers of the Fe.EDTA-proteins corresponding to GCN4 residues 222 to 281 and 226 to 281 revealed that the NH2-termini were in the major groove nine to ten base pairs apart and were symmetrically displaced four to five base pairs from the central C of the recognition site [36].
  • The CD28-responsive complex bound to the IL-2 gene between -164 and -154 base pairs from the transcription start site [37].
  • Like RecA, RAD51 also appears to force DNA into a conformation of approximately a 5.1-angstrom rise per base pair and 18.6 base pairs per turn [38].

Analytical, diagnostic and therapeutic context of Base Pairing


  1. Recognition of a TG mismatch: the crystal structure of very short patch repair endonuclease in complex with a DNA duplex. Tsutakawa, S.E., Jingami, H., Morikawa, K. Cell (1999) [Pubmed]
  2. An antitermination protein engages the elongating transcription apparatus at a promoter-proximal recognition site. Barik, S., Ghosh, B., Whalen, W., Lazinski, D., Das, A. Cell (1987) [Pubmed]
  3. HIV-1 Rev regulation involves recognition of non-Watson-Crick base pairs in viral RNA. Bartel, D.P., Zapp, M.L., Green, M.R., Szostak, J.W. Cell (1991) [Pubmed]
  4. A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes. Thorlacius, S., Olafsdottir, G., Tryggvadottir, L., Neuhausen, S., Jonasson, J.G., Tavtigian, S.V., Tulinius, H., Ogmundsdottir, H.M., Eyfjörd, J.E. Nat. Genet. (1996) [Pubmed]
  5. Sequence of inverted terminal repetitions from different adenoviruses: demonstration of conserved sequences and homology between SA7 termini and SV40 DNA. Tolun, A., Aleström, P., Pettersson, U. Cell (1979) [Pubmed]
  6. Structural consequences of a carcinogenic alkylation lesion on DNA: effect of O6-ethylguanine on the molecular structure of the d(CGC[e6G]AATTCGCG)-netropsin complex. Sriram, M., van der Marel, G.A., Roelen, H.L., van Boom, J.H., Wang, A.H. Biochemistry (1992) [Pubmed]
  7. A novel mutation in the beta-protein coding region of the amyloid beta-protein precursor (APP) gene. Balbín, M., Abrahamson, M., Gustafson, L., Nilsson, K., Brun, A., Grubb, A. Hum. Genet. (1992) [Pubmed]
  8. Polymorphism of the rat liver mitochondrial aldehyde dehydrogenase cDNA. Carr, L.G., Mellencamp, R.J., Crabb, D.W., Weiner, H., Lumeng, L., Li, T.K. Alcohol. Clin. Exp. Res. (1991) [Pubmed]
  9. Active site tightness and substrate fit in DNA replication. Kool, E.T. Annu. Rev. Biochem. (2002) [Pubmed]
  10. Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Bagga, S., Bracht, J., Hunter, S., Massirer, K., Holtz, J., Eachus, R., Pasquinelli, A.E. Cell (2005) [Pubmed]
  11. Block of HAC1 mRNA translation by long-range base pairing is released by cytoplasmic splicing upon induction of the unfolded protein response. Rüegsegger, U., Leber, J.H., Walter, P. Cell (2001) [Pubmed]
  12. Efficient and accurate replication in the presence of 7,8-dihydro-8-oxoguanine by DNA polymerase eta. Haracska, L., Yu, S.L., Johnson, R.E., Prakash, L., Prakash, S. Nat. Genet. (2000) [Pubmed]
  13. Spontaneous functional correction of homozygous fanconi anaemia alleles reveals novel mechanistic basis for reverse mosaicism. Waisfisz, Q., Morgan, N.V., Savino, M., de Winter, J.P., van Berkel, C.G., Hoatlin, M.E., Ianzano, L., Gibson, R.A., Arwert, F., Savoia, A., Mathew, C.G., Pronk, J.C., Joenje, H. Nat. Genet. (1999) [Pubmed]
  14. Analysis of regulatory elements involved in the induction of two tobacco genes by salicylate treatment and virus infection. Van de Rhee, M.D., Van Kan, J.A., González-Jaén, M.T., Bol, J.F. Plant Cell (1990) [Pubmed]
  15. The vinyl chloride DNA derivative N2,3-ethenoguanine produces G----A transitions in Escherichia coli. Cheng, K.C., Preston, B.D., Cahill, D.S., Dosanjh, M.K., Singer, B., Loeb, L.A. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  16. Wide cross-species aminoacyl-tRNA synthetase replacement in vivo: yeast cytoplasmic alanine enzyme replaced by human polymyositis serum antigen. Ripmaster, T.L., Shiba, K., Schimmel, P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  17. Oligonucleotide sequence signaling transcriptional termination of vaccinia virus early genes. Yuen, L., Moss, B. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  18. Assembly of core helices and rapid tertiary folding of a small bacterial group I ribozyme. Rangan, P., Masquida, B., Westhof, E., Woodson, S.A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  19. Analysis of nutR: a region of phage lambda required for antitermination of transcription. Olson, E.R., Flamm, E.L., Friedman, D.I. Cell (1982) [Pubmed]
  20. A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cawthon, R.M., Weiss, R., Xu, G.F., Viskochil, D., Culver, M., Stevens, J., Robertson, M., Dunn, D., Gesteland, R., O'Connell, P. Cell (1990) [Pubmed]
  21. Post-transcriptional regulatory mutants in a ribosomal protein-RNA polymerase operon of E. coli. Fiil, N.P., Friesen, J.D., Downing, W.L., Dennis, P.P. Cell (1980) [Pubmed]
  22. Direct repeats flank three small nuclear RNA pseudogenes in the human genome. Van Arsdell, S.W., Denison, R.A., Bernstein, L.B., Weiner, A.M., Manser, T., Gesteland, R.F. Cell (1981) [Pubmed]
  23. A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid. Mullan, M., Crawford, F., Axelman, K., Houlden, H., Lilius, L., Winblad, B., Lannfelt, L. Nat. Genet. (1992) [Pubmed]
  24. The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Yoshida, H., Hayashi, S., Kunisada, T., Ogawa, M., Nishikawa, S., Okamura, H., Sudo, T., Shultz, L.D., Nishikawa, S. Nature (1990) [Pubmed]
  25. Neuregulins are concentrated at nerve-muscle synapses and activate ACh-receptor gene expression. Jo, S.A., Zhu, X., Marchionni, M.A., Burden, S.J. Nature (1995) [Pubmed]
  26. Conformational changes of U6 RNA during the spliceosome cycle: an intramolecular helix is essential both for initiating the U4-U6 interaction and for the first step of slicing. Wolff, T., Bindereif, A. Genes Dev. (1993) [Pubmed]
  27. Reaction of systemic lupus erythematosus antinative DNA antibodies with native DNA fragments from 20 to 1,200 base pairs. Papalian, M., Lafer, E., Wong, R., Stollar, B.D. J. Clin. Invest. (1980) [Pubmed]
  28. Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita. Ptácek, L.J., George, A.L., Barchi, R.L., Griggs, R.C., Riggs, J.E., Robertson, M., Leppert, M.F. Neuron (1992) [Pubmed]
  29. Chimeric gRNA-mRNA molecules with oligo(U) tails covalently linked at sites of RNA editing suggest that U addition occurs by transesterification. Blum, B., Sturm, N.R., Simpson, A.M., Simpson, L. Cell (1991) [Pubmed]
  30. The crystal structure of HaeIII methyltransferase convalently complexed to DNA: an extrahelical cytosine and rearranged base pairing. Reinisch, K.M., Chen, L., Verdine, G.L., Lipscomb, W.N. Cell (1995) [Pubmed]
  31. An unwinding activity that covalently modifies its double-stranded RNA substrate. Bass, B.L., Weintraub, H. Cell (1988) [Pubmed]
  32. A stretch of "late" SV40 viral DNA about 400 bp long which includes the origin of replication is specifically exposed in SV40 minichromosomes. Varshavsky, A.J., Sundin, O., Bohn, M. Cell (1979) [Pubmed]
  33. A structural basis for S1 nuclease sensitivity of double-stranded DNA. Pulleyblank, D.E., Haniford, D.B., Morgan, A.R. Cell (1985) [Pubmed]
  34. Mutations in U1 snRNA bypass the requirement for a cell type-specific RNA splicing factor. Nandabalan, K., Price, L., Roeder, G.S. Cell (1993) [Pubmed]
  35. Cloning and characterization of a new intercellular adhesion molecule ICAM-R. Vazeux, R., Hoffman, P.A., Tomita, J.K., Dickinson, E.S., Jasman, R.L., St John, T., Gallatin, W.M. Nature (1992) [Pubmed]
  36. Structural motif of the GCN4 DNA binding domain characterized by affinity cleaving. Oakley, M.G., Dervan, P.B. Science (1990) [Pubmed]
  37. Regulation of interleukin-2 gene enhancer activity by the T cell accessory molecule CD28. Fraser, J.D., Irving, B.A., Crabtree, G.R., Weiss, A. Science (1991) [Pubmed]
  38. Similarity of the yeast RAD51 filament to the bacterial RecA filament. Ogawa, T., Yu, X., Shinohara, A., Egelman, E.H. Science (1993) [Pubmed]
  39. Glucocorticoid and progesterone receptors bind to the same sites in two hormonally regulated promoters. von der Ahe, D., Janich, S., Scheidereit, C., Renkawitz, R., Schütz, G., Beato, M. Nature (1985) [Pubmed]
  40. Characterization of the Caenorhabditis elegans Tc1 transposase in vivo and in vitro. Vos, J.C., van Luenen, H.G., Plasterk, R.H. Genes Dev. (1993) [Pubmed]
  41. Suppressors of trp1 fluorescence identify a new arabidopsis gene, TRP4, encoding the anthranilate synthase beta subunit. Niyogi, K.K., Last, R.L., Fink, G.R., Keith, B. Plant Cell (1993) [Pubmed]
  42. Nucleic acid duplexes incorporating a dissociable covalent base pair. Gao, K., Orgel, L.E. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  43. Genetic recombination can generate altered restriction specificity. Fuller-Pace, F.V., Bullas, L.R., Delius, H., Murray, N.E. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
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