V.S.RAVIKIRAN, MSc.

DEOXYNUCLEIC ACID (DNA)

V.S.RAVIKIRAN, MSc., Department of Biochemistry,

ASRAM Medical college, Eluru-534005.AP, India.vsravikiran2013@gmail.c

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NUCLEIC ACIDSV.S.RAVIKIRAN

The “central dogma” of Molecular Biology

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NUCLEIC ACIDS: INFORMATIONAL POLYMER

• Nucleic acids are polymers of monomer units called nucleotides

• Nucleic acids store and transmit hereditary information: gene

• Two major forms of nucleic acid polymers: DNA and RNA

DNA(Deoxyribonucleic Acid)

DNA Structure

DNA is a nucleic acid.The building blocks of DNA are nucleotides,

each composed of:– a 5-carbon sugar called deoxyribose– a phosphate group (PO4)

– a nitrogenous base• adenine, thymine, cytosine, guanine

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DNA Structure

The nucleotide structure consists of– the nitrogenous base attached to the 1’ carbon of

deoxyribose– the phosphate group attached to the 5’ carbon of

deoxyribose– a free hydroxyl group (-OH) at the 3’ carbon of

deoxyribose

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DNA Structure

Nucleotides are connected to each other to form a long chain

phosphodiester bond: bond between adjacent nucleotides– formed between the phosphate group of one

nucleotide and the 3’ –OH of the next nucleotideThe chain of nucleotides has a 5’ to 3’

orientation.

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DNA Structure

Determining the 3-dimmensional structure of DNA involved the work of a few scientists:

– Erwin Chargaff determined that • amount of adenine = amount of thymine• amount of cytosine = amount of guanine

This is known as Chargaff’s Rules

Chargaff

DNA Structure

Rosalind Franklin and Maurice Wilkins– Franklin performed X-ray diffraction studies to

identify the 3-D structure– discovered that DNA is helical– discovered that the molecule has a diameter of

2nm and makes a complete turn of the helix every 3.4 nm

Franklin

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DNA Structure

James Watson and Francis Crick, 1953– deduced the structure of DNA using evidence

from Chargaff, Franklin, and others– proposed a double helix structure

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DNA Structure

The double helix consists of:– 2 sugar-phosphate backbones– nitrogenous bases toward the interior of the

molecule– bases form hydrogen bonds with complementary

bases on the opposite sugar-phosphate backbone

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DNA Structure

The two strands of nucleotides are antiparallel to each other– one is oriented 5’ to 3’, the other 3’ to 5’

The two strands wrap around each other to create the helical shape of the molecule.

Double Helix• 2 complementary strands of DNA

– sugar-phosphate backbone– nitrogenous bases stacked in the center– antiparallel

• 5’ end• 3’ end

– twists to right

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Base Pairing in DNA: The Watson-Crick Model

According to the Watson–Crick model, a DNA molecule consists of two polynucleotide strands coiled around each other in a helical, screwlike fashion.

The sugar–phosphate backbone is on the outside of this right-handed double helix, and the heterocyclic bases are on the inside, so that a base on one strand points directly toward a base on the second strand.

The double helix resembles a twisted ladder, with the sugar–phosphate backbone making up the sides and the hydrogen-bonded base pairs, the rungs.

AT

GC

TA

CG

CG

GC

AT

Chargaff’s Rules• base pairing

rules– A=T– C G

Prentice Hall © 2007 Chapter Twenty Six 40

Hydrogen bonds connect the pairs of bases; thymine with adenine, cytosine with guanine.

Structure of DNA

DNA double Helix

Chargaff’s rules: the amount of adenine equals the amount of thymine, and the amount of guanine equals the amount of cytosine, and the total amount of purines equals the total amount of pyrimidine.

Hydrogen bonds between complementary basesFORMAMIDE, ANNEALING

The three helical forms of DNA (and RNA)

PhysiologicalDNA

Very unusualDNA

RNAHigh-salt

DNA

Type Shape Helix Base pair per turn

Pitch per bp

Width Occurrence

A Broadest Righthanded

11 0.256 nm 2.3 nm High saltMedium

B Intermediate

Righthanded

10 0.338 nm 1.9 nm NormalForm

Z Elongated Lefthanded

12 0.571 nm 1.8 nm Some ofDNA

B-form DNA consists of a right-handed double helix with antiparallel strands

34 Å (10 bp) per turn

major groove

minor groovemajor groove

minor

3.4 Å per bp

These dimensions are for DNA fibers. In solution, there are ~10.5 base-pairs per turn.

5’ 3’

5’3’

Pharm201 Lecture 2 2007 50

V o e t, D o n a ld a n d Ju d ith G . B io c h e mis try.Jo h n Wile y & S o n s , 1 9 9 0 , p . 8 0 0 .

Canonical A DNA

Pharm201 Lecture 2 2007 51

Z-DNA

Summary of the main structural features of B-form DNA

•Right-handed helix

•Two antiparallel strands held together by

Watson-Crick hydrogen bonds

•Pitch (repeat length) = 34 Å (3.4 nm)

•36o rotation between residues

•Helix diameter of 20 Å (2.0 nm)

•Wide major groove, narrow minor groove

•Chargaff’s Rules: A = T; G = C

•Charged phosphates

•Bases in anti configuration

•The strands separate at high temperatures

•The solution structure is dynamic

DNA

• Functions• 1. Storage of genetic information• 2. Self-duplication & inheritance.• 3. Expression of the genetic message.• DNA’s major function is to code for proteins.• Information is encoded in the order of the

nitrogenous bases.

Figure 11.6

DNAdoublehelix(2-nmdiameter)

Metaphase chromosome

700nm

Tight helical fiber(30-nm diameter)

Nucleosome(10-nm diameter)

Histones

“Beads ona string”

Supercoil(200-nm diameter)

HISTONES

H1, H2A, H2B, H3, H4