DNA Structure & Chemistry - Harvard University

DNA Structure

& Chemistry

Goal

To understand the structure

and chemistry of DNA and

the significance of the double

helix.

Objectives

After this chapter, you should be able to

? explain the structural basis for the

directionality of polynucleotide chains.

? describe how hydrogen bonding and

geometry dictate base pairing.

? describe the forces that stabilize the

DNA double helix.

? explain the significance of the grooves

in the DNA double helix.

? describe how DNA is compacted into

chromosomes.

8

Proteins, as we have seen, are the workhorses of the cell; they exhibit

extraordinarily varied structures, which enable them to perform myriad

tasks. This is in sharp contrast to deoxyribonucleic acid (DNA) molecules,

which with few exceptions exhibit a single, common structure: the double

helix. This makes sense because DNA has just one function, information

storage. Just as a compact disc can contain the blueprint for building a

house, DNA is a storage depot for the information needed to make the

diverse proteins of the cell. The instructions for specifying the primary

structure of a protein are stored in a stretch of DNA known as a gene.

Almost all of the carbon-containing molecules in living systems are either

proteins that are directly encoded by DNA or non-protein molecules that

are generated by the actions of enzymes, which like other proteins are

themselves specified by DNA. In Chapters 8-12 we will learn how the cell

replicates DNA molecules and does so faithfully, how it retrieves genetic

information to direct the synthesis of proteins, and how it regulates this

flow of genetic information from DNA to protein. But first, in this chapter

we look closely at the structure and chemistry of DNA in order to learn how

its double-helical architecture allows information to be stored, duplicated,

and accessed.

Each DNA strand is an alternating copolymer of phosphates and

deoxyribose sugars

As its name implies, the double helix is composed of two polynucleotide

chains that are wrapped around each other as helices. We focus first on the

Chapter 8

DNA Structure & Chemistry

Figure 1 DNA is an alternating

polymer of

phosphate

deoxyribose

Base

and

P

Base

Deoxyribose

P

Deoxyribose

chemical nature of the individual chains. Each is a copolymer composed

alternately of phosphate groups and sugar units (Figure 1). The sugar units

HO 5¡¯

are pivotal to the chains, as the four nucleobases (or more simply bases),

OH

which we will consider soon, are attached to the sugars. The sugars are

O

4¡¯

1¡¯

pentose sugars, meaning that they contain five carbon atoms. The positions

3¡¯

of the carbons in the sugars are labeled with apostrophes, which are referred

2¡¯

to as primes (1¡¯-5¡¯), to distinguish them from the numbering of positions

HO

in the bases (Figure 2). The bases are attached to the sugars at the 1¡¯ (¡°one2¡¯-deoxyribose

prime¡±) position via a glycosidic linkage (simply meaning that the base

is bonded to a sugar). Notice that the sugars are five-membered rings in

Figure 2 The carbon atoms in which an oxygen atom links the 1¡¯ and 4¡¯ carbons. Notice also that the 5¡¯

deoxyribose are numbered 1¡¯ to 5¡¯ carbon is off the ring, being attached to it via the 4¡¯ carbon. Thus, only four

of the five carbons contribute to the five-membered ring.

The sugars in DNA are 2¡¯-deoxyribose sugars in that the carbon at position

2¡¯ lacks a hydroxyl group and instead has two hydrogen atoms. RNA, which

we will consider in a later chapter, is a similar copolymer, but its sugars are

ribose sugars, which contain a hydroxyl group at the 2¡¯ position in place of

one of the two hydrogen atoms.

Importantly, the phosphates in the alternating copolymer are joined to the

sugars at the 3¡¯ and 5¡¯ positions via phosphate ester linkages (in which

a phosphorous atom double-bonded to oxygen is joined to a carboncontaining group via a second oxygen atom) (Figure 3). Because the

phosphates are joined to the sugars through two ester linkages, these are

said to be phosphodiester bonds.

Figure 3 Phosphodiester linkages

connect the 3¡¯ carbon of one

deoxyribose sugar to the 5¡¯ carbon

of the adjacent sugar in the DNA

polymer

O 5¡¯

Base

O

3¡¯

O

O

P

O

O 5¡¯

O

Base

3¡¯

O

O

O

P

O 5¡¯

3¡¯

O

O

Base

2

Chapter 8

DNA Structure & Chemistry

Box 1 Nucleotides are tripartite repeating units in polynucleotides

We have so far presented the polynucleotide chain as an alternating copolymer of phosphates and deoxyribose

sugars to which bases are attached. An alternative way to think about the chain is as a simple polymer of

units consisting of a phosphate, a sugar, and a base. Such tripartite units are referred to as nucleotides,

hence the name polynucleotide. Nucleotides in DNA have a single phosphate, but free nucleotides can

have two or three (and sometimes more) phosphate groups. Nucleotides bearing three phosphates at the 5¡¯

position of deoxyribose will become important in subsequent chapters when we consider the biosynthesis

of polynucleotide chains. A bipartite structure consisting of a sugar and a base but no phosphates is referred

to as a nucleoside.

Figure 4 Polynucleotides are also

polymers of nucleotides

Shown is a single nucleotide within a DNA

double helix and its three-dimensional stick

representation as well as a corresponding

standard line drawing. Atoms in the

three-dimensional structure are colored

as follows: carbon, green; oxygen, red;

nitrogen, blue; phosphorus, orange.

5¡¯

4¡¯

3¡¯

2¡¯

1¡¯

Base

O

O P O

Phosphate

O

O

NH2

N

O

N

N

N

Sugar

Polynucleotide chains have a 5¡¯-to-3¡¯ directionality and align in an antiparallel orientation in the double helix

A fundamental feature of the polynucleotide chain is that its ends are

dissimilar. Thus, the 3¡¯ hydroxyl is displayed at one terminus, the 3¡¯ end,

and the 5¡¯ hydroxyl at the other terminus, the 5¡¯ end. This means that

polynucleotide chains have an intrinsic directionality. This is analogous to

the directionality of polypeptide chains, which, as we have seen, have an

N-terminus and a C-terminus.

Since the double helix consists of two polynucleotide strands, what is the

orientation of the two helical strands relative to each other? The answer

is that the two strands are oriented such that the 5¡¯-to-3¡¯ directionality of

one strand aligns with the 3¡¯-to-5¡¯ directionality of the other strand. That

the directionality of the two strands is anti-parallel is an invariant rule that

governs the interaction of polynucleotide chains (RNA as well as DNA)

with each other.

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Chapter 8

DNA Structure & Chemistry

3¡¯

5¡¯

5¡¯

3¡¯

O

O Base

O

O

P

O

Base

O

O

O

O

O

P

O

Base

O

O

P

O

O P

O

Base

3¡¯

O

O

O

O

O

Base

O

Base

T

C

A

C

A

G

T

G

3¡¯

5¡¯

DNA strands are antiparallel

O P

O

O

O

Base

O

3¡¯

3¡¯

5¡¯

O

Base

O

O

P

O

O

O

O

O

O

5¡¯

5¡¯

Figure 5 Polynucleotide chains are antiparallel in the double helix

A:T and C:G are abbreviations for the bases and their pairing (adenine paired with thymine and cytosine paired with guanine), as we

come to next.

As we will consider in detail in later chapters, the directionality of

polynucleotides and of polypeptides is the basis for three foundational rules

that govern the duplication and retrieval of genetic information. These

are that: (1) the synthesis of polynucleotide chains always proceeds in a

5¡¯-to-3¡¯ direction, (2) the synthesis of polypeptide chains always proceeds

in an N-to-C-terminal direction, and (3) the information for amino acid

sequences from the N-terminal amino acid to the C-terminal amino acid is

specified sequentially in a 5¡¯-to-3¡¯ direction in polynucleotide chains.

The two strands of the double helix interact with each other via two pairs

of complementary bases

Each deoxyribose in the polynucleotide chain is attached to one of four

bases that mediate interactions between the two strands of the double helix.

Bases are flat rings consisting of carbon and nitrogen atoms; they are said to

be heterocyclic because they are composed of rings containing other atoms

than just carbon. There are two kinds of bases, pyrimidines and purines.

Pyrimidines are single, six-membered heterocyclic rings, whereas purines

have a bicyclic structure consisting of five- and six-membered heterocyclic

rings. The positions of carbon and nitrogen atoms in the pyrimidine and

purine rings are numbered as shown in Figure 6. Pyrimidines are joined

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Chapter 8

DNA Structure & Chemistry

7

N

6

5

4

8

9

N

H

5

N1

N

4

2

6

3

NH2

NH2

N

N

N

NH

N

2

Pyrimidine

O

N

H

N

1

Purine

N

N3

N

H

NH2

Guanine

N

H

N

Adenine

O

NH

N

H

O

O

Thymine

Cytosine

Figure 6 The bases are purines and pyrimidines

The four bases in DNA belong to two families whose numbering systems are shown.

via a glycosidic linkage to the 1¡¯ position of deoxyribose via the nitrogen at

position 1, whereas purines are attached via the nitrogen at position 9.

The pyrimidines are cytosine (C) and thymine (T), and the purines are

adenine (A) and guanine (G) (Figure 6). Base pairs consist of a pyrimidine

and a purine such that cytosine pairs uniquely with guanine (C:G) and

thymine specifically with adenine (T:A) (Figure 7). (As we will see in

Chapter 10, RNA contains the pyrimidine uracil in place of thymine; like

thymine, uracil pairs with adenine.) Compared to the 20 disparate side

chains of amino acids, the four bases are relatively similar-looking. In

contrast to side chains, however, they all principally do one thing: pair with

a single complementary base.

(A)

A

O

O N

O

H

N

(B)

Thymine

Adenine

N

T

O

N H

H N

N

Guanine

O

O

N

O

O N

O

O

N

G

O

N

H

O

T

H N

N H

N

N H

O

H Cytosine

C

O

N

O

O

C

G

A

9.0 ?

9.0 ?

Figure 7 Each base specifically pairs with one other base

Adenine and thymine form two complementary hydrogen bonds to form the A:T base pair (A), whereas guanine and cytosine form three

complementary hydrogen bonds to form the G:C base pair (B). Both the A:T and G:C base pairs have the same width, as shown in orange.

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