Chargaffs rules

The base composition of a nucleic acid can be determined quite simply by digesting the DNA or RNA with non-spedfic phosphodiesterases and analysing the nudeotide or nucleoside products combined treatment with Serratia marcescens nuclease (i.e., Benzonase ) and PI nuclease yields nudeoside-5 -monophosphates. Further treatment with alkaline phosphatase leads to dephosphorylation and the formation of nucleosides that can be analysed by RP-HPLC. This procedure can also be used to detect and quantitate modified nucleotides and nucleosides. The base composition of double stranded nucleic acids follows the well known Chargaff rules ... 

Chargaff rule the amount of adenine and thymine in DNA is equal the amount of cytosine and guanine are equal. (A = T, C = G). The amount of purines equals the amount of pyrimidines. 

These quantitative relationships, sometimes called Chargaffs rules, were confirmed by many subsequent researchers. They were a key to establishing the three-dimensional structure of DNA and yielded clues to how genetic information is encoded in DNA and passed from one generation to the next. 

These results break the pseudo-ChargafF rule observed in the rest of the genome - G and C do not behave similarly, and nor do A and T. This can occur because the two DNA strands are distinct in exonic regions, with only one of them being transcribed to form RNA. However, that does not explain why such a marked decrease in G-patterns is observed. 

One curious feature of DNA was noted by Erwin Chargaff, who carefully studied the chemical composition of nucleic acids from many different biological species. There was a surprisingly wide variation in the actual percentages of A, G, C and T between different species, but, oddly enough, the percentage of G was always very close to that of C, and that of A to that of T. Chargaffs rule offered a massive clue, but no one apparently spotted what it meant at the time. 

According to the Chargaff rule, each nucleic acid has as much adenine as thymine (Table 29-4). There are also equal amounts of guanine and cytosine or 5-methyl cytosine. Because of this, the term base pairing of A/T, G/C, G/5MC, and A/ U is used. The rule applies well to DNA, but there are often significant deviations in the case of RNA. This difference is closely related to the differences in physical structure between DNA and RNA (see also Section 29.4). 

Ribonucleic acids are unbranched molecules. In contrast to DNA, they are mostly single-stranded molecules. But the ribonucleic acids of some viruses are double stranded. Only some of the bases are paired, and these are intramolecularly paired, and not intermolecularly, as is the case for DNA (Figure 29-3). The only partial base pairing explains the frequent deviations of RNAs from the Chargaff rule, since it is not necessary to have every purine base paired with a pyrimidine partner for the conformation to be thermodynamically stable. RNAs adopt a compact elliptical shape. 

Naturally occurring nucleic acids contain equal amounts of adenine and thymine (Table 29-3) and equal amounts of guanine and cytosine (or 5-methyl cytosine) (Chargaff rule). DNA follows this rule well, whereas for RNA there are often significant deviations. This difference between DNA and RNA is a consequence of their structural differences (see Sections 29.4.1 and 29.4.2). 

Molar Ratios Leading to the Formulation of Chargaff s Rules ... 

The Watson-Crick double helix is the outcome of three lines of work. The first is the discovery by Erwin Chargaff of Chargaff s rules." Specifically, for all normal DNAs, A = T, G = C and A + G = C + T. The actual content of each base in DNA varies from species to species over a wide range. Despite this variation, the content... 

Chargaff s rules were first defined in E. Chargaff, Experientia 6 201-209 (1950). 

Erwin Chargaff found that the ratios of adenine to thymine and of guanine to cytosine were always 1 1, suggesting that these bases form pairs. The fact that the ratios are 1 1 is referred to as Chargaff s rules. 

Chargaff s Studies of DNA Structure The chapter section DNA Is a Double Helix that Stores Genetic Information includes a summary of the main findings of Erwin Chargaff and his coworkers, listed as four conclusions ( Chargaff s rules p. 278). In this problem, you will examine the data Chargaff collected in support of these conclusions. 

The explanation for Chargaff s rules is provided by die selective hydrogen bonds, termed complementary base pairing, that form between adenine and thymine molecules and between guanine and cytosine. Adenine and thymine form two hydrogen bonds with an overall strength of about 10 kcal/mol (42 kJ/mol) ... 

Erwin Chargaff s discovery that DNA contains equimolar amounts of guanine and cytosine and also equimolar amounts of adenine and thymine has come to be known as Chargaff s rule ... 

These complementarity rules owe their discovery to the chemical analysis of DNA by Chargaff and associates (3). The DNA from many different organisms shows the same patterns of base composition, namely A and T are always present in equal quantities, as are G and C. The immediate corollary of this observation, that a purine base (R) exists for every pyrimidine base (Y) and vice versa, led Watson and Crick to propose that two helical strands in DNA are held together by specific, intermolecular purine-pyrimidine (R Y) interactions (4). In turn, this unique chemical complementarity of the double-helical structure, proved to be a major breakthrough to understand the self-recognition and self-reproduction of DNA and forms the cornerstone of structmal biology as we know it today, more than half a century later. 

The 1 1 ratios of adenine Thymine and guaninexytosine in the DNA isolated from a wide variety of species investigated by Erwin Chargaff between 1948 and 1952. (This relationship is sometimes referred to as Chargaff s rules.)... 

According to Chargaff s rules, if a DNA sample contains 21% adenine then it also contains 21% thymine. If the A-T content is 42%, then the G-C content is 58%. Consequently the guanine and cytosine percentages are both 29% in the DNA sample. 

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