molecular biology of the gene dna structure and function

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Molecular Biology of the Gene DNA Structure and Function

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Page 1: Molecular Biology of the Gene DNA Structure and Function

Molecular Biology of the GeneDNA Structure and Function

Page 2: Molecular Biology of the Gene DNA Structure and Function

History of DNA• 1869 Johann Friedrich Miescher

• 1924 Microscope studies using stains for DNA and protein show that both substances are present in chromosomes.

• 1952 Alfred Hershey and Martha Chase

Page 3: Molecular Biology of the Gene DNA Structure and Function

SCIENTIFIC DISCOVERY: DNA is a double-stranded helix

Erwin Chargaff

Rosalind Franklin / Maurice Wilkins

James Watson and Francis Crick

In 1962, the Nobel Prize

Page 4: Molecular Biology of the Gene DNA Structure and Function

SCIENTIFIC DISCOVERY: Experiments showed that DNA is the genetic material

Until the 1940s, the case for proteins serving as the genetic material was stronger than the case for DNA.

– Proteins are made from ____different amino acids.

– DNA was known to be made from just ____ kinds of nucleotides.

Studies of bacteria and viruses

– ushered in the field of molecular biology, the study of heredity at the molecular level, and

– revealed the role of DNA in heredity.

Page 5: Molecular Biology of the Gene DNA Structure and Function

DNA and RNA are polymers of nucleotides

DNA and RNA are nucleic acids.

The building blocks or monomers of nucleic acids are ____________________

A nucleotide is composed of a

– _________________

– _________________

– __________________

The nucleotides are joined to one another by a bond creating the sugar-phosphate backbone.

Page 6: Molecular Biology of the Gene DNA Structure and Function
Page 7: Molecular Biology of the Gene DNA Structure and Function

A

A

A

A

A

A

A

C

T

T

T

T

T

T

C

C

C

C

G

G

G

G

G

C

C G

AT

A DNAdouble helix

T

DNAnucleotide

Covalentbondjoiningnucleotides

A

C

T

Two representationsof a DNA polynucleotide

G

G

G

G

C

T

Phosphategroup

Sugar(deoxyribose)

DNA nucleotide

Thymine (T)

Nitrogenous base(can be A, G, C, or T)

Sugar

Nitrogenousbase

Phosphategroup

Sugar-phosphatebackbone

Page 8: Molecular Biology of the Gene DNA Structure and Function

4 Different Types of Nucleotides Found in DNA

Page 9: Molecular Biology of the Gene DNA Structure and Function

Base pair

Hydrogen bond

Partial chemicalstructure

Computermodel

Ribbonmodel

Page 11: Molecular Biology of the Gene DNA Structure and Function

Purine or pyrimidine ?

Hydrogen bonds hold the 2 strands together

Page 12: Molecular Biology of the Gene DNA Structure and Function

2 General Functions for DNA

1.

2.

Page 13: Molecular Biology of the Gene DNA Structure and Function

DNA replication depends on specific base pairing

In their description of the structure of DNA, Watson and Crick noted that the structure of DNA suggests a possible copying mechanism.

DNA replication follows a semiconservative model.

Page 14: Molecular Biology of the Gene DNA Structure and Function

DNA Replication

SEMICONSERVATIVE

1. Helix unwinds

2. 2 strands separate

3. Free nucleotides bind to open bases according to pairing rules

(parent strand acts as template)

4. 2 identical strands consist of one parent strand and one newly formed strand.

Page 15: Molecular Biology of the Gene DNA Structure and Function

DNA replication begins at the origins of replication where

– DNA unwinds at the origin to produce a “bubble,”

– replication proceeds in both directions from the origin, and

– replication ends when products from the bubbles merge with each other.

DNA replication occurs in the 5 to 3 direction.– Replication is continuous on the 3 to 5 template.– Replication is discontinuous on the 5 to 3 template,

forming short segments.

DNA replication proceeds in two directions at many sites simultaneously

Page 16: Molecular Biology of the Gene DNA Structure and Function

Leading and Lagging strands

Why? DNA polymerases can only assemble new strands in the 5’-> 3’ direction, need a 3’ end

(-OH) provided by RNA primer.

Page 17: Molecular Biology of the Gene DNA Structure and Function
Page 18: Molecular Biology of the Gene DNA Structure and Function

Overall direction of replication

DNA ligase

Replication fork

Parental DNA

DNA polymerasemolecule This daughter

strand is synthesizedcontinuously

This daughterstrand is synthesizedin pieces

35

35

3

5

35

Page 19: Molecular Biology of the Gene DNA Structure and Function

DNA replication proceeds in two directions at many sites simultaneously

Key proteins are involved in DNA replication.

– Helicase

– DNA Polymerases-

– Primase

– Proofreader

– DNA ligase

Page 20: Molecular Biology of the Gene DNA Structure and Function

ParentalDNAmolecule Origin of

replication

“Bubble”

Parental strand

Daughter strand

TwodaughterDNAmolecules

Page 21: Molecular Biology of the Gene DNA Structure and Function

http://207.207.4.198/pub/flash/24/menu.swf

ANIMATION…Replication

http://highered.mcgraw-hill.com/olc/dl/120076/bio23.swf

http://www.phschool.com/science/biology_place/biocoach/dnarep/intro.html

Page 22: Molecular Biology of the Gene DNA Structure and Function

DNA Repair

Page 23: Molecular Biology of the Gene DNA Structure and Function

DNA processes

• Replication

• Protein Synthesis

–Transcription

–Translation

Page 24: Molecular Biology of the Gene DNA Structure and Function

Protein Functions….

• Metabolism (enzymes are proteins)

• Structural (build form)

• Transport (ex- hemoglobin)

• Protection (antibodies are proteins)

• Cell communication (hormones)

Page 25: Molecular Biology of the Gene DNA Structure and Function

Review of Protein Structure…

Only 20 different common amino acids

Structure determines function !

Hundreds of thousands of different proteins !

Page 26: Molecular Biology of the Gene DNA Structure and Function

The DNA genotype is expressed as proteins, which provide the molecular basis for

phenotypic traits

DNA specifies traits by dictating protein synthesis.

The molecular chain of command is from

– DNA in the nucleus to RNA and

– RNA in the cytoplasm to protein.

__________________ is the synthesis of RNA under the direction of DNA.

__________________ is the synthesis of proteins under the direction of RNA.

Page 27: Molecular Biology of the Gene DNA Structure and Function

3 parts of RNA (the other nucleic acid) nucleotide

sugar = _________

phosphate group

nitrogenous base (A,U,C,G)

U=Uracil

Nucleotides: 2 types DNA & RNA

Page 28: Molecular Biology of the Gene DNA Structure and Function

3 Types of RNA Required for Protein Synthesis

• mRNA= messenger RNA

• tRNA= transfer RNA

• rRNA= ribosomal RNA

Page 29: Molecular Biology of the Gene DNA Structure and Function

DNA

NUCLEUS

CYTOPLASM

RNA

Transcription

Translation

Protein

Page 30: Molecular Biology of the Gene DNA Structure and Function

T

Strand to be transcribed

A C T T C AA

A A A T

DNAAA T C

T T T T G A G G

RNA

Transcription

A A A A U U U U U G G G

Translation

Polypeptide Met Lys Phe

Stopcodon

Startcodon

Page 31: Molecular Biology of the Gene DNA Structure and Function

The DNA genotype is expressed as proteins, which provide the molecular basis for

phenotypic traits

The connections between genes and proteins

– The initial one gene–one enzyme hypothesis was based on studies of inherited metabolic diseases.

– The one gene–one enzyme hypothesis was expanded to include all proteins.

– Most recently, the one gene–one polypeptide hypothesis recognizes that some proteins are composed of multiple polypeptides.

Page 32: Molecular Biology of the Gene DNA Structure and Function

Transcription- overview

Transcribing (writing) information from DNA

Takes place in the nucleus

Promoter region is recognized by RNA polymerase as a start location

Assembles mRNA strand

mRNA

Page 33: Molecular Biology of the Gene DNA Structure and Function

RNApolymerase

Free RNAnucleotides

Templatestrand of DNA

Newly made RNA

Direction oftranscription

TG

AG G

A

A

U C C AC

T TA

A

CC

GGU

T UTAACCT

A

TC

TRANSCRIPTION

Page 34: Molecular Biology of the Gene DNA Structure and Function

RNA polymerase

DNA of gene

PromoterDNA

Initiation1

2

TerminatorDNA

3

Elongation Area shownin Figure 10.9A

TerminationGrowingRNA

RNApolymerase

CompletedRNA

Page 35: Molecular Biology of the Gene DNA Structure and Function

Genetic information written in codons is translated into amino acid sequences

The sequence of nucleotides in DNA provides a code for constructing a protein.

Page 36: Molecular Biology of the Gene DNA Structure and Function

Transcription produces genetic messages in the form of RNA

Overview of transcription

– An RNA molecule is transcribed from a DNA template by a process that resembles the synthesis of a DNA strand during DNA replication.

– RNA nucleotides are linked by the transcription enzyme RNA polymerase.

– Specific sequences of nucleotides along the DNA mark where transcription begins and ends.

– The “start transcribing” signal is a nucleotide sequence called a promoter.

Page 37: Molecular Biology of the Gene DNA Structure and Function

Transcription produces genetic messages in the form of RNA

– Transcription begins with initiation, as the RNA polymerase attaches to the promoter.

– During the second phase, elongation, the RNA grows longer.

– As the RNA peels away, the DNA strands rejoin.

– Finally, in the third phase, termination, the RNA polymerase reaches a sequence of bases in the DNA template called a terminator, which signals the end of the gene.

– The polymerase molecule now detaches from the RNA molecule and the gene.

Page 38: Molecular Biology of the Gene DNA Structure and Function

DNA

Cap

Exon Intron Exon

RNAtranscriptwith capand tail

ExonIntron

TranscriptionAddition of cap and tail

Introns removed Tail

Exons spliced together

Coding sequenceNUCLEUS

CYTOPLASM

mRNA

POST-TRANSCRIPTIONAL MODIFICATION

Page 39: Molecular Biology of the Gene DNA Structure and Function

Eukaryotic mRNA

– RNA splicing

– Additions- cap and tail

Post-Transcriptional Modification:Eukaryotic RNA is processed

before leaving the nucleus as mRNA

Page 40: Molecular Biology of the Gene DNA Structure and Function

Post-Transcriptional Modification:Eukaryotic RNA is processed

before leaving the nucleus as mRNA

Messenger RNA (mRNA)

– encodes amino acid sequences and

– conveys genetic messages from DNA to the translation machinery of the cell, which in

– prokaryotes, occurs in the same place that mRNA is made, but in

– eukaryotes, mRNA must exit the nucleus via nuclear pores to enter the cytoplasm.

– Eukaryotic mRNA has

– introns, interrupting sequences that separate

– exons, the coding regions.

Page 41: Molecular Biology of the Gene DNA Structure and Function

Genetic information written in codons is translated into amino acid sequences

The flow of information from gene to protein is based on a triplet code: the genetic instructions for the amino acid sequence of a polypeptide chain are written in DNA and RNA as a series of nonoverlapping three-base “words” called codons.

Each amino acid is specified by a codon.– 64 codons are possible.

– Some amino acids have more than one possible codon.

Page 42: Molecular Biology of the Gene DNA Structure and Function

Transfer RNA molecules serve as interpreters during translation

Transfer RNA (tRNA)

Page 43: Molecular Biology of the Gene DNA Structure and Function

Ribosomes build polypeptides

rRNA and proteins make up the ribosome.

Translation occurs on the surface of the ribosome

Page 44: Molecular Biology of the Gene DNA Structure and Function

The genetic code dictates how codons are translated into amino acids

Characteristics of the genetic code

– _______ nucleotides specify one amino acid.

– 61 codons correspond to amino acids.

– AUG is the start codon; codes for methionine and signals the start of transcription.

– 3 “stop” codons signal the end of translation; _____, ____, ____

– __________- with more than one codon for some amino acids

– _______________- the genetic code is shared by organisms from the simplest bacteria to the most complex plants and animals

Page 45: Molecular Biology of the Gene DNA Structure and Function

GENETIC CODE

Page 46: Molecular Biology of the Gene DNA Structure and Function

Practice

• DNA is TACAGGCGATGGATT

• mRNA is ____________________

• Divide into codons (reading frames)

• Amino acids coded for are:

Page 47: Molecular Biology of the Gene DNA Structure and Function

An initiation codon marks the start of an mRNA message (Initiation)

Translation can be divided into the same three phases as transcription:

1. initiation,

2. elongation, and

3. termination.

Initiation brings together…

Page 48: Molecular Biology of the Gene DNA Structure and Function

An initiation codon marks the start of an mRNA message (Initiation)

Initiation establishes where translation will begin.

Initiation occurs in two steps.

1. An mRNA molecule binds to a small ribosomal subunit and the first tRNA binds to mRNA at the start codon.

– The start codon reads AUG and codes for methionine.

– The first tRNA has the anticodon UAC.

2. A large ribosomal subunit joins the small subunit, allowing the ribosome to function.

– The first tRNA occupies the P site, which will hold the growing peptide chain.

– The A site is available to receive the next tRNA.

Page 49: Molecular Biology of the Gene DNA Structure and Function

Elongation adds amino acids to the polypeptide chain

Once initiation is complete, amino acids are added one by one to the first amino acid.

Elongation is the addition of amino acids to the polypeptide chain.

Page 50: Molecular Biology of the Gene DNA Structure and Function

Each cycle of elongation has three steps.

1. Codon recognition: The anticodon of an incoming tRNA molecule, carrying its amino acid, pairs with the mRNA codon in the A site of the ribosome.

2. Peptide bond formation: The new amino acid is joined to the chain.

3. Translocation: tRNA is released from the P site and the ribosome moves tRNA from the A site into the P site.

Elongation adds amino acids to the polypeptide chain

Page 51: Molecular Biology of the Gene DNA Structure and Function

Polypeptide

mRNA

Codon recognition

Anticodon

Aminoacid

Codons

Psite

Asite

1

Peptide bond2

formation

Translocation3

Newpeptidebond

Stopcodon

mRNAmovement

Elongation

Page 52: Molecular Biology of the Gene DNA Structure and Function

Termination stage of translation, when– the ribosome reaches a stop codon,

– the completed polypeptide is freed from the last tRNA, and

– the ribosome splits back into its separate subunits.

Elongation adds amino acids to the polypeptide chain

until a stop codon; Termination

Page 53: Molecular Biology of the Gene DNA Structure and Function

Other Helpful Animations….

http://highered.mcgraw-hill.com/sites (there are selections at this site that will help with replication, transcription and translation)

Page 54: Molecular Biology of the Gene DNA Structure and Function

DNATranscription

mRNARNApolymerase

Transcription

Translation

Amino acid

Enzyme

CYTOPLASM

Amino acidattachment

2

1

3

4

tRNA

ATP

Anticodon

Initiation ofpolypeptide synthesis

Elongation

Largeribosomalsubunit

InitiatortRNA

Start Codon

mRNA

Growingpolypeptide

Smallribosomalsubunit

New peptidebond forming

Codons

mRNA

Polypeptide

Termination5

Stop codon

Review: The flow of Geneticinformation in the cell is

DNA

RNA

Protein

Page 55: Molecular Biology of the Gene DNA Structure and Function

Mutations can change the meaning of genes

A mutation is any change in the nucleotide sequence of DNA.

Mutations can involve

– large chromosomal regions or

– just a single nucleotide pair.

Mutations can be spontaneous (mistakes during replication) or caused by mutagens.

Examples- UV light, chemicals

Page 56: Molecular Biology of the Gene DNA Structure and Function

. A mutation can be:– Harmful, giving rise to cancers.– Cause genetic disorders (if in sperm or egg)

– Create new traits/variation

in the species

Mutations can change the meaning of genes

Page 57: Molecular Biology of the Gene DNA Structure and Function

Normal hemoglobin DNA Mutant hemoglobin DNA

mRNA mRNA

Sickle-cell hemoglobinNormal hemoglobin

Glu Val

C T T

G A A

C T

G A

A

U

Page 58: Molecular Biology of the Gene DNA Structure and Function

Normalgene

Nucleotidesubstitution

Nucleotidedeletion

Nucleotideinsertion

Inserted

Deleted

mRNAProtein Met

Met

Lys Phe

Lys Phe

Ala

Ala

Gly

Ser

A U G A A G U U U G G C G C A

G C G C AAG U U UA U G A A

Met Lys Ala HisLeu

G U UA U G A A G G C G C A U

U

Met Lys Ala HisLeu

G U UA U G A A G G CU G G C

Page 59: Molecular Biology of the Gene DNA Structure and Function

1. Compare the structures of DNA and RNA.

2. State the contributions of Chargaff, Franklin, Wilkins, Watson and Crick to our understanding of DNA.

3. Describe the process of DNA replication. State the role of helicase, DNA polymerases, primase, and DNA ligase

4. Describe the general purpose of protein synthesis; relate DNA sequence to the specific protein produced.

You should now be able to

Page 60: Molecular Biology of the Gene DNA Structure and Function

5. State the general flow of genetic information as genes are expressed.

6. Explain transcription and how mRNA is produced using DNA.

7. Explain how eukaryotic RNA is processed before leaving the nucleus.

8. Discuss the role of mRNA, tRNA and rRNA in translation.

9. Explain translation; initiation, elongation, translocation and termination.

You should now be able to

Page 61: Molecular Biology of the Gene DNA Structure and Function

10. Describe the structure and function of ribosomes

11. .Define mutation, causes of mutations, and potential consequences.

12. State the amino acid sequence in a polypeptide given the mRNA.

You should now be able to

© 2012 Pearson Education, Inc.

Page 62: Molecular Biology of the Gene DNA Structure and Function

DNA

(b)

is a polymermade from

monomers called

is performedby an

enzyme called(c)

(a)

(d)

(e)

(f)

comesin three

kinds called

use amino-acid-bearingmolecules called

is performedby structures

called (h)

molecules arecomponents of

RNA

Protein

(g)

(i)one or more polymers

made frommonomers called