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The bend here is produced by four (dA)5 tracts, separated by five basepairs. The adenine bases are shown in red.337Chapter 12 Nucleotides and Nucleic AcidsFigure 12—20 Palindromes and mirror repeats.Palindromes are defined in nucleic acids as sequences with twofold symmetry. In order to superimpose one repeat (shaded sequence) on the other,it must be rotated 180° around the horizontal axisand then again about the vertical axis, as shown bythe colored arrows.
A mirror repeat, on the otherhand, has a symmetric sequence on each strand.Superimposing one repeat on the other requiresonly a single 180° rotation about the vertical axis.PalindromeT T A G C A C G T G CI1I 1 I I 1T AA~I1A A T C G T G C A C G A T TMirror repeatT T A G C A C C A C G A T TII l I I I l l l l I I IlA A T C G T G G T G C T A AA rather common type of sequence found in DNA is a palindrome.A palindrome is a word, phrase, or sentence that is spelled identicallyreading forward or backward; two examples are ROTATOR andNURSES RUN. The term is applied to regions of DNA in which thereare inverted repetitions of base sequence with twofold symmetryoccurring over two strands of DNA (Fig. 12-20).
Such sequences areself-complementary within each of the strands and therefore have thepotential to form hairpin or cruciform (cross-shaped) structures (Fig.12-21). When the inverted sequence occurs within each individualstrand of the DNA, the sequence is called a mirror repeat. Mirrorrepeats do not have complementary sequences within the same strandand cannot form hairpin or cruciform structures. Sequences of thesetypes are found in virtually every large DNA molecule and can involvea few or up to thousands of base pairs. It is not known how manypalindromes actually occur as cruciforms in cells, although the existence of at least some cruciform structures has been demonstrated invivo in E. coli. Self-complementary sequences cause isolated singlestrands of DNA to fold up in solution into complex structures containing multiple hairpins.A particularly unusual DNA structure, known as H-DNA, is foundin polypyrimidine/polypurine tracts that also incorporate a mirror repeat within the sequence.
One simple example is a long stretch of alternating T and C residues, as shown in Figure 12-22. A novel feature ofH-DNA is the pairing and interwinding of three strands of DNA to forma triple helix. Triple-helical DNA forms spontaneously only within longsequences containing only pyrimidines (or only purines) in one strand.Two of the three strands in the H-DNA triple helix (Fig. 12-22c, d)contain pyrimidines and the third contains purines.These structural variations are interesting because there is a tendency for many of them to appear at sites where important events inDNA metabolism (replication, recombination, transcription) are initi-TGCGATACTCATCGCAI IIITTATCGCA3'TAGCGTI IITTHairpin(a)ACGCTACTCATAGCGTI IIIIIIII II III11I11I1I1IIiII1I1 1TGCGATGAGTATCGCA£!£TAGCGTATCGCAI III IIFigure 12-21 Hairpins and cruciforms.
Palindromic DNA (or RNA) sequences can form alternativestructures with intrastrand base pairing. Whenonly a single DNA (or RNA) strand is involved it iscalled a hairpin (a). When both strands of a duplexDNA are involved, the structure is called a cruciform (b). Blue shading highlights asymmetric sequences that can pair alternatively with a complementary sequence in the same or opposite strand.-•51I I I1 1 1TGCGATACGCTACruciform(b)-•5 1338Part II Structure and CatalysisTriple helixc3' •••CCTGTCCAGAGAGAGAGAGAGAG-Av\TG: */ TCTCTCTCTCTCTCTC-T-CAA G A G A G A G A G A G A G A G- A-"(a)(b)(c)ated or regulated.
For example, the sites recognized by many sequencespecific DNA-binding proteins (Chapter 27) are arranged as palin*dromes, and sequences that can form H-DNA are found within regionsinvolved in the regulation of expression of a number of genes in eu~karyotes. Much work is still required to define these structures anddetermine their functional significance.Messenger RNAs Code for Polypeptide ChainsFigure 12-22 H-DNA. A sequence of alternating Tand C residues can be considered a mirror repeatcentered about one of the central T or C residues(a). These sequences form an unusual structure inwhich the strands in one half of the mirror repeatare separated, and the pyrimidine-containingstrand folds back on the other half of the repeat toform a triple helix (b).
The purine strand (alternating A and G residues) is left unpaired. This structure produces a sharp bend in the DNA. (c) Atriple-helical DNA formed from two pyrimidinestrands (polydeoxythymidine, shown with gray andlight blue backbones) and one purine strand(polydeoxyadenine, with a dark blue backbone).Phosphorus atoms are shown in yellow. In thisstructure the light blue and dark blue strands areantiparallel and paired via normal Watson-Crickbase pairing patterns. The third (gray) strand isparallel to the dark blue (purine) strand and pairedthrough non-Watson-Crick hydrogen bonds, including one between the C-4 carbonyl group of thymine and the N-7 of adenine.
(d) An end view ofthe triple-helical DNA shown in (c), with the basetriplet at one end.We now turn our attention briefly from DNA structure to the expression of the genetic information contained in DNA. RNA, the secondmajor form of nucleic acid in cells, plays the role of intermediary inconverting this information into a functional protein.In eukaryotes DNA is largely confined to the nucleus, whereas protein synthesis occurs on ribosomes in the cytoplasm. Therefore somtmolecule other than DNA must carry the genetic message for proteinsynthesis from the nucleus to the cytoplasm. As early as the 1950s*:RNA was considered the logical candidate: RNA is found in both thenucleus and cytoplasm, and the onset of protein synthesis is accompa?nied by an increase in the amount of RNA in the cytoplasm and afiincrease in its rate of turnover.
These and other observations led sev*eral researchers to suggest that RNA carries genetic information fronfDNA to the protein biosynthetic machinery of the ribosome. In 1961^Francois Jacob and Jacques Monod presented a unified (and essen*tially correct) picture of many aspects of this process. They propose!the name messenger RNA (mRNA) for that portion of the total cellRNA carrying the genetic information from DNA to the ribosome^where the messengers provide the templates for specifying amino misequences in polypeptide chains.
Although mRNAs from different!genes can vary greatly in length, the mRNAs from a particular gene:will generally have a defined size. The process of forming mRNA on aDNA template is known as transcription.Chapter 12 Nucleotides and Nucleic Acids3395'Figure 12—23 Schematic diagram of monocistronic(a) and polycistronic (b) mRNAs of prokaryotes.The polycistronic transcript shown here containsthree genes. Noncoding RNA separates the genes.5'NoncodingRNARNA coding fora gene productGene 1NoncodingRNARNA coding fora gene productGene 1NoncodingRNA3'(a)RNA coding fora second geneproductGene 2In prokaryotes a single mRNA molecule may code for one or several polypeptide chains.
If it carries the code for only one polypeptide,the mRNA is monocistronic; if it codes for two or more different polypeptides, the mRNA is polycistronic. In eukaryotes, most mRNAsare monocistronic. (The term cistron, for purposes of this discussion,refers to a gene. The term itself has historical roots in the science ofgenetics, and its formal genetic definition is beyond the scope of thistext.) The minimum length of an mRNA is set by the length of thepolypeptide chain for which it codes.
For example, a polypeptide chainof 100 amino acid residues requires an RNA coding sequence of at least300 nucleotides, because each amino acid is coded by a nucleotide triplet (Chapter 26). However, mRNAs transcribed from DNA are alwayssomewhat longer than needed simply to specify the code for the polypeptide sequence(s). The additional noncoding RNA includes sequences that regulate protein synthesis (Chapter 26).
Figure 12-23summarizes the general structure of prokaryotic mRNAs.NoncodingRNARNA coding fora third geneproductGene 33'(b)Many RNAs Have More Complex StructuresMessenger RNA is only one of several classes of cellular RNA. TransferRNAs serve as adapter molecules in protein synthesis; covalentlylinked to an amino acid at one end, they pair with the mRNA in such away that the amino acids are joined in the correct sequence. RibosomalRNAs are structural components of ribosomes.
There is also a widevariety of special-function RNAs. All of these are considered in detailin Chapter 25.Regardless of the class of RNA being synthesized, the product oftranscription is always a single strand of RNA. The single-strandednature of these molecules does not mean their structure is random.The single strands tend to take up a right-handed helical conformationthat is dominated by base-stacking interactions (Fig. 12-24). Thestacking interactions are stronger between two purines than betweena purine and a pyrimidine or between two pyrimidines. The purinepurine interaction is so strong that a pyrimidine separating two purines will often be displaced from the stacking pattern so that the purines can interact.
Any self-complementary sequences in the moleculewill lead to more complex and specific structures. RNA can base-pairwith complementary strands of either RNA or DNA. The standardbase-pairing rules are identical to those for DNA: guanine pairs withcytosine and adenine pairs with uracil (or thymine). One difference isthat one unusual base pairing—between guanine and uracil—is fairlycommon between two strands of RNA; see Fig. 12-26.
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