dogma sentra

1

Chapter IV Genetics

DNA and Protein Synthesis

Yalun Arifin

Basic definitions

DNA: The molecule that encodes genetic information. DNA is a double-stranded molecule held together by weak bonds between base pairs of nucleotides. The four nucleotides in DNA contain the bases: adenine (A), guanine (G), cytosine (C), and thymine (T). In nature, base pairs form only between A and T and between G and C; thus the base sequence of each single strand can be deduced from that of its partner.

RNA: A chemical found in the nucleus and cytoplasm of cells; it plays an important role in protein synthesis and other chemical activities of the cell. The structure of RNA is similar to that of DNA. There are several classes of RNA molecules, including messenger RNA, transfer RNA, ribosomal RNA, and other small RNAs, each serving a different purpose.

DNA and RNA

Biochemistry of DNA

Double Helix

Two DNA strands are antiparallel.

Held together by base pairs:

•Hydrogen bonds between the nitrogen-containing bases

•A = T, and G = C

DNA Structure Reveals Key to Replication

Each of the two original strands serves as a template for construction of a new matching strand.

DNA and RNA

In RNA, thymine is replaced by uracil

Nucleotides joined by covalent bonds between sugar and phosphate to make a chain

Bases are laid out in specific and highly varied order, carrying code for protein synthesis

P

S

P

S

P

S

G

T

A

A

C

T

S

P

S

P

S

P

DNA

G C

Nucleotide A T SP

SPSPSS

PP

SP

SPSPSS

PP

SP

SPSPSS

PP

SP

SPSPSS

PP

A T

C GO

O

OO

O

OG C

T A

A T

G C

T A

A T

A

C G

A T

A T

T A

G C

DNA: Central dogma

Central dogma in cells

In the absence of a nuclear membrane, DNA Transcription and RNA Translation are not physically separated.

DNA undergoes replication and transcription in the nucleus; proteins are made in the cytoplasm. RNA must therefore travel across the nuclear membrane before it is translated: transcription and translation are physically separated. The primary transcript, heterogeneous RNA (hnRNA), undergoes extensive post-transcriptional processing to make mRNA.

How do DNA keep the information?

The genetic information in DNA in kept in the sequences of bases in the nucleotides (A ,T, G, C). This code consists of 3 nucletiodes (e.g. ATG, AAA, TAA) that encodes a certain amino acid. Thus, 64 codes are possible to give the infinite number of genetic sequences.

DNA ReplicationNew helices are composed of half old (original) and half new nucleotides.

Process catalyzed by enzymes:

•DNA polymerase catalyzes addition of matching bases, and proofreads.

•DNA ligase permanently attaches short sections to make one chromosome.

• Proteins: Polypeptides – Strands of amino acids (20 different) joined by peptide

bonds.

– Every protein has a unique amino acid sequence.

Protein SynthesisHow Proteins Are Made: Genetic Transcription, Translation, and Regulation

gly

ile

val

glu

gln

cys

cys asn

cys

tyr

asn

glu

ala

ser

val

cys

ser

leu

tyr

gln

leu

H

C

H

H3N CO

O–

glycine (gly)

C

H

H3N CO

O–CH

CH2

CH3

isoleucine

H3N CO

O–

• Protein Synthesis: Two Stages– Stage 1—DNA contains information for protein but

resides in the nucleus; proteins are made in the cytoplasm. Solution: Copy DNA into small strands of RNA (transcription).

– Stage 2—Amino acids added in correct order by using the information on the RNA (translation).

OVERVIEW OF TRANSCRIPTION AND TRANSLATION

DNA

mRNA

TRANSCRIPTION(in nucleus)

ribosomes

mRNA

protein

TRANSLATION(in cytoplasm)

tRNA

RNA strand DNA strand

C

UG C

A T

C

G

AU

UC

C

C

G

G

A

A

T

T

A T

CG

SP

PS

SP

PS

S

SP

PS

SP

PS

S

RNA nucleotide DNA nucleotide

sugar-phosphatehandrail

Bases: cytosine (C) guanine (G) adenine (A) uracil (U)

Bases: cytosine (C) guanine (G) adenine (A) thymine (T)

sugar-phosphatehandrail

SP

PS

SP

PS

S

O O

H H3C C

N

N

HOH

C

N

NH

O

O

H

HH

OH

H

O

O

H

HH

OH

ribose(sugar)

uracil(base)

CH2OPHO

O

O–

CH2OPHO

O

O–

Phosphate group

Phosphate group

thymine(base)

deoxyribose(sugar)

Basic definitionsIntron: The DNA base sequences interrupting the protein- coding sequences of a gene; these sequences are transcribed into RNA but are cut out of the message before it is translated into protein.

Exons: the sequences in the DNA molecule that code for the amino acid sequences of corresponding proteins.

Messenger RNA: the template for protein synthesis; the form of RNA that carries information from DNA in the nucleus to the ribosome sites of protein synthesis in the cell

Transfer RNA: short-chain RNA molecules present in the cell (in at least 20 varieties, each variety capable of combining with a specific amino acid) that attach the correct amino acid to the protein chain that is being synthesized at the ribosome of the cell (according to directions coded in the mRNA)

Ribosomal RNA: RNA found in ribosome

• Three Types of RNA Transcribed– mRNA (messenger RNA) carries instructions for

sequence of amino acids in a protein.

– rRNA (ribosomal RNA) important component of ribosomes.

– tRNA (transfer RNA) involved in matching correct amino acid to specific instructions in mRNA.

Table 14.2Types of RNA

Type of RNA Functions in Function

Messenger RNA(mRNA)

Nucleus, migratesto ribosomesin cytoplasm

Carries DNA sequenceinformation to ribosomes

Transfer RNA(tRNA)

Cytoplasm Provides linkage between mRNAand amino acids;transfers aminoacids to ribosomes

Ribosomal RNA(rRNA)

Cytoplasm Structural component of ribosomes

• Transcription Uses Base Pairing– DNA used as a template to match complementary

bases.

– C to G and A to U (not T).

– RNA polymerase catalyzes addition of new nucleotides into a single strand of RNA (called a transcript) from one strand of the double helix.

mRNAC G UU AC

G C A A G T A CC T G A

mRNA

mRNA

DNA

RNA nucleotides

UG G

A C U

• RNA Processing– mRNA is edited.

– Parts to be cut out are called introns.

– The remaining pieces (called exons) are joined together to make the finished product.

exon 1 INTRON exon 2 INTRON exon 3

enzyme

enzymes cut into the introns

edited mRNA transcript

• Making Sense of “Junk” DNA– Only 1.5% of our DNA codes for proteins (1 inch out

of 6 feet).

– Rest is noncoding DNA—housekeeping (regulatory) sequences, tips of chromosomes, and “junk”:

• Introns

• Repetitive Sequences “Selfish DNA” Primates have 1 million Alu (280 base pairs long) repeats, 10%

of DNA, congregate in gene-rich areas.

• Genetic Code: How DNA Codes for Amino Acid Sequence– Four bases in DNA, 20 amino acids in protein, not one-

to-one code.

– Not two to one either—There are only 16 possible combinations of two bases of DNA (AA, AT, AC, AG, CA, etc.).

– Triplet code—three nucleotides (called a codon) signifying one amino acid.

THE TRIPLET CODE

DNA

mRNA

protein arg ser trp thr

codon codon codon codonC G U U C A U G G A C U

G C A A G T A C C T G A

TRANSCRIPTION

TRANSCRIPTION

• Codon Table– 64 different possible combinations of the four

nucleotides—more than enough for the 20 different amino acids.

– Redundant = several different codons signify the same amino acid.

– Carries instruction codons for stopping (UGA, UAA, UAG) and starting (AUG) translation.

– Universal

U C A G

U

C

A

G

GACU

GACU

GACU

GACU

UUUUUCUUAUUG

CUUCUCCUACUG

AUUAUCAUAAUG

GUUGUCGUAGUG

phe

leu

leu

ile

met (start)

val

UCUUCCUCAUCG

CCUCCCCCACCG

ACUACCACAACG

GCUGCCGCAGCG

ser

pro

thr

ala

UAUUACUAAUAG

CAUCACCAACAG

AAUAAC

AAGAAA

GAUGACGAAGAG

tyr

stopstop

his

gln

asn

lys

asp

glu

UGUUGCUGAUGG

CGUCGCCGACGG

AGUAGCAGAAGG

GGUGGCGGAGGG

cys

stoptrp

arg

ser

arg

gly

Firs

t B

ase

Third

Base

Second Base

• Translation Requires Translator– mRNA carries the instructions in the codons for each of

the amino acids.

– tRNA molecules (transfer RNA) are “translator” molecule.

– tRNA can match the appropriate amino acid with the codon in the mRNA.

mRNA

ribosome

glythrgluleuser

phe

asp

tyr

• Structure of Transfer RNA– Part of the molecule binds an amino acid.

– The other end has three nucleotides (anticodon) that form a base pair with the codon in the mRNA.

amino acid

amino acid attached site

tRNA molecule

G CU

anticodon

C AG

mRNA attachment site

codonmRNA

• Ribosomes: The Location of Protein Synthesis– Large conglomerate of enzymes and ribosomal RNA

(rRNA) in two subunits.

– A site—binds tRNA-carrying amino acids.

– P site—binds tRNA attached to growing chain of polypeptides.

mRNA

protein

large subunit

small subunit

protein

mRNA

large subunit

small subunit

P A

Psite

Asite

• Steps of Translation

met met

metmet

leu

mRNA

start codon

AUG

CUG

Psite

Asite

Psite

Asite

GAC

leu

UCA

met leu

met

metleu

leu

Psite

Asite

thr

Psite

Asite

Psite

Asite

Polypeptide chain

• Genetic Regulation: Lac Operon– Operon = multipart genetic system.

– Bacteria (E. coli) synthesize certain enzymes only if substrate is present.

– Example—lactose, called an inducer

– Genes involved: • y (permease enzyme to help lactose enter the cell)

• z (-galactosidase enzyme to cut lactose into galactose and glucose)

• a gene

• i (codes for repressor protein)

codes for repressor protein

regulator gene

i gene p o z gene y gene a gene DNA

lac operon

promotoroperator

binding siteof RNApolymerase

codes for permease enzymethat transportslactose into cells

codes for-galactoseidase,which clipslactose molecules

• Lac Operon: Regulatory DNA Sequences– Upstream promoter (acts as a binding site for RNA

polymerase)

– Between promoter and first gene is operator.

– Repressor binds operator: prevents RNA polymerase from binding to the promoter.

– No transcription, so no enzymes made.


repressorprotein

repressor protein blocks binding of RNA polymerase

RNA polymerase

no transcription

• Lac Operon: Lactose Inducer Present– Cell needs to make enyzmes only when lactose is

present.

– Repressor binds lactose; it will not bind the operator, so transcription ensues.


repressor

lactose

galactose glucose

-galactosidase

mRNA transcript

transcription proceeds3

cell membrane

lactose

RNA polymerasebinds to promoter

2

lactose the (inducer)inactivates the repressorso that it cannot bind to the operator

1

permease

• Magnitude of Metabolic Operations– Human cells have between 50,000 and 100,000 genes.

– But one cell usually makes only 5,000 to 20,000 specifically required proteins.

– Some are made continuously, and others are inducible.

dogma sentra

Documents