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1. DNA was dicovered by Juhann Friedrich in 18692. And the first demonstration that DNA contain genetic

information was made in 1944 by Avery, Macleod and MacCary

3. 1951—Rosalind Franklin was showed or explained the —X-ray crystallography of DNA

4. 1953 Watson & Crick—explained complet stru. Of DNA

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1) DNA is composed of 2 chains of nucleotides that form a double helix shape.

2) The two strands are antiparallel.

3) The backbone of the DNA molecule is composed of alternating phosphate groups and sugars.

4) The complimentary nitrogenous bases form hydrogen bonds between the strands.

5) A is complimentary to T and G is complimentary to C.

6) The Diameter is 20 A(2nm)

7) The 2 polynucleotide chains are not identical but complimentary to each other.

8) The hydrogen bonds formed between purine and pyrimidine only.

9) The DNA is write handed double helix.

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Synthetic Nucleotide analogs & Chemotherapy

Synthetic analogs of purines, pyrimidines, nucleosides, and nucleotides altered in either the heterocyclic ring or the sugar moiety.

1. The purine analog allopurinol, used in treatment of hyperuricemia and gout.

2. Cytarabine is used in chemotherapy of cancer.3. Azathioprine is employed during organ transplantation

to suppress immunologic rejection.

phenotype

Protein

DNA

Gene

Trait

Gene

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Genes & ProteinsGenes & Proteins• DNA contains genes, sequences of nucleotide

bases

• These Genes code for polypeptides (proteins)

• Proteins are used to build cells and do much of the work inside cells

• Proteins are made of amino acids linked together by peptide bonds

• 20 different amino acids exist

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DNA Begins the ProcessDNA Begins the Process• DNA is found inside the nucleus• Proteins, however, are made in the

cytoplasm of cells by organelles called ribosomes

• Ribosomes may be free in the cytosol or attached to the surface of rough ER

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Starting with DNAStarting with DNA

• DNA ‘s codeDNA ‘s code must be must be copiedcopied and taken and taken to the cytosolto the cytosol

• In the cytoplasm, this In the cytoplasm, this code must be code must be readread so so amino acidsamino acids can be assembled can be assembled to make polypeptides (proteins)to make polypeptides (proteins)

• This process is called This process is called PROTEIN PROTEIN SYNTHESISSYNTHESIS

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Roles of RNA and DNA

• DNA is the MASTER PLAN

• RNA is the BLUEPRINT of the Master Plan

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RNA Differs from DNARNA Differs from DNA

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Other DifferencesOther Differences

• RNA contains the RNA contains the base base uracil (Uuracil (U))DNA has DNA has thymine thymine (T)(T)

• RNA molecule is RNA molecule is single-strandedsingle-strandedDNA is DNA is double-double-strandedstranded

15DNA

Three Types of RNAThree Types of RNA• Messenger RNA (mRNA)Messenger RNA (mRNA) copies copies

DNA’s code & carries the genetic DNA’s code & carries the genetic information to the ribosomesinformation to the ribosomes

• Ribosomal RNA (rRNA)Ribosomal RNA (rRNA), along , along with protein, makes up the with protein, makes up the ribosomesribosomes

• Transfer RNA (tRNA)Transfer RNA (tRNA) transfers transfers amino acids to the ribosomes amino acids to the ribosomes where proteins are synthesizedwhere proteins are synthesized

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Messenger RNAMessenger RNA• Long Straight chain of Nucleotides

• Made in the Nucleus

• Copies DNA & leaves through nuclear pores

• Carries the information for a Carries the information for a specific proteinspecific protein

• Made up of Made up of 500 to 1000 nucleotides long500 to 1000 nucleotides long

• Sequence of 3 bases called Sequence of 3 bases called codoncodon

• AUGAUG – methionine or – methionine or start codonstart codon

• UAA, UAG, or UGAUAA, UAG, or UGA – – stop codonsstop codons

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Ribosomal RNA (rRNA)Ribosomal RNA (rRNA)

• rRNA is a single strand rRNA is a single strand 100 to 100 to 3000 nucleotides3000 nucleotides long long

• GlobularGlobular in shape in shape• Made inside the Made inside the nucleusnucleus of a cell of a cell• Associates with Associates with proteins to form proteins to form

ribosomesribosomes• Site of Site of protein Synthesisprotein Synthesis

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The Genetic Code

• A codon designates an amino acid

• An amino acid may have more than one codon

• There are 20 amino acids, but 64 possible codons

• Some codons tell the ribosome to stop translating

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Name the Amino Acids

• AG?• UCA?

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Remember the Complementary Remember the Complementary BasesBases

On DNA: A-T C-GOn RNA: A-U C-G

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Transfer RNA Transfer RNA (tRNA)(tRNA)

• Clover-leaf shape

• Single stranded molecule with attachment site at one end for an amino acid

• Opposite end has three nucleotide bases called the anticodon

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Codons and Codons and AnticodonsAnticodons

• The 3 bases of an anticodon are complementary to the 3 bases of a codon• Example: Codon ACU Anticodon UGA

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UGAACU

Transcription and Transcription and TranslationTranslation

TranscriptionTranscription

• The process of copying the sequence of one strand of DNA, the template strand

• mRNA copies the template strand

• Requires the enzyme RNA Polymerase

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Question:Question:

What would be the What would be the complementary RNA complementary RNA strand for the following strand for the following DNA sequence?DNA sequence?

DNA 5’-DNA 5’-GCGTATGGCGTATG-3’-3’

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TranscriptionTranscription

• Consists of three stages

– Initiation: attachment of RNA Polymerase to the promotor region on DNA

– Elongation: building of the mRNA from the 3’ end of the nucleotide polymer

– Termination: release of RNA polymerase and mRNA following transcription of the terminator region of the DNA

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1. Initiation

• Genes on the DNA begin with a promoter region consisting of a sequence of A & T (TATA box)

• Transcription factors (proteins that assist the binding of RNA polymerase to the promoter) are found in association with the promoter region

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Elongation

• Once initiation is complete the 2 strands of the DNA unwind due to the zipper region of the enzyme.

• RNA polymerase builds a mRNA strand complimentary to the DNA transcription unit.

• Once the RNA Polymerase passes the DNA strands reform their double helix

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Termination In Eukaryotes

• The transcribed termination sequence, also known as the polyadenylation signal in the pre-mRNA, is AAUAAA.

• Polymerase continues to synthesize RNA until an enzyme catches up to it and causes it too fall off.

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• Transcribed mRNA (pre-mRNA) must be modified before leaving the nucleus

• modifications include:– addition guanine triphosphate cap to the 5” end of the mRNA

• Prevents “unraveling” • Helps ribosome attach

– addition of poly A tail to the 3’ end of the mRNA• Prevents “unraveling”• Assists in the export of mRNA from nucleus

Modification of mRNA

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TailNew Transcript

Result of TranscriptionResult of Transcription

How is this done?• Small nuclear

ribonucleicproteins (snRNP) recognize intron ends and together with proteins form a structure called a spliceosome

• Spliceosomes remove introns while connecting exons together

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Why bother with introns?

1) Introns may regulate gene activity and the passage of mRNA into the cytoplasm

2) Genes may play roles in multiple proteins, introns may enable a gene to be diverse in function

3) May increase recombination of genetic material (easier to cut and paste)

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Translation

A. Translation-forming of a polypeptide

-uses mRNA as a template for a.a. sequence

-steps (initiation, elongation, translocation and termination)

-begins after mRNA enters cytoplasm

-uses tRNA (the interpreter of mRNA)

B. Ribosomes

-made of proteins and rRNA-each has a large and small subunit-each has three or two binding sites for tRNA on its surface-each has one binding site for mRNA-facilitates codon and anticodon bonding

Translation

-The three tRNA binding sites are:

1. A site=holds tRNA that is carrying the next amino acid to be added

2. P site= holds tRNA that is carrying the growing polypeptide chain

3. E site= where discharged tRNAs leave the ribosome

Translation

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– 61 of 64 codons code for a.a.– Codon AUG has two functions

1. codes for amino acid methionine (Met)2. functions as a start codon

– mRNA codon AUG starts translation– three codons act as stop codons (end translation)

Translation

A. (Initiation)

1. Brings together mRNA, tRNA (w/ 1st a.a.) and ribosomal subunits

2. Small ribosomal subunit binds to mRNA and an initiator tRNA

-start codon= AUG- anticodon-UAC-small ribosomal subunit attaches to 5’ end of mRNA

-downstream from the 5’ end is the start codon AUG (mRNA)-the anticodon UAC carries the a.a. Methionine

3. After the union of mRNA, tRNA and small subunit, the large ribosomal subunit attaches.

• The intitiator tRNA and a.a. will sit in the P site of the large ribosomal subunit

• The A site will remain vacant and ready for the aminoacyl-tRNA

Translation (Initiation)

B. (Elongation)Amino acids are added one by one to the first amino acid (remember, the goal is to make a polypeptide)Step 1: Codon recognition

mRNA codon in the A site forms hydrogen bonds with the tRNA anitcodon

Step 2- Peptide bond formationThe ribosome catalyzes the formation of the peptide bonds between the amino acids (the one already in place and the one being added)The polypeptide extending from the P site moves to the A site to attach to the new amino acid.

1. The tRNA with the polypeptide chain in the A site is translocated to the P site

2. tRNA at the P site moves to the E site and leaves the ribosome

3. The ribosome moves down the mRNA in the 5’→3’ direction

Translation (Translocation)

InitiationInitiation

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mRNAmRNA

A U G C U A C U U C G

2-tRNA

G

aa2

A U

A

1-tRNA

U A C

aa1

anticodon

hydrogenbonds codon

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mRNAmRNA

A U G C U A C U U C G

1-tRNA 2-tRNA

U A C G

aa1 aa2

A UA

anticodon

hydrogenbonds codon

peptide bond

3-tRNA

G A A

aa3

ElongationElongation

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mRNAmRNA

A U G C U A C U U C G

1-tRNA

2-tRNA

U A C

G

aa1

aa2

A UA

peptide bond

3-tRNA

G A A

aa3

Ribosomes move over one codon

(leaves)

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mRNAmRNA

A U G C U A C U U C G

2-tRNA

G

aa1

aa2

A UA

peptide bonds

3-tRNA

G A A

aa3

4-tRNA

G C U

aa4

A C U

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mRNAmRNA

A U G C U A C U U C G

2-tRNA

G

aa1aa2

A U

A

peptide bonds

3-tRNA

G A A

aa3

4-tRNA

G C U

aa4

A C U

(leaves)

Ribosomes move over one codon

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mRNAmRNA

G C U A C U U C G

aa1aa2

A

peptide bonds

3-tRNA

G A A

aa3

4-tRNA

G C U

aa4

A C U

U G A

5-tRNA

aa5

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mRNAmRNA

G C U A C U U C G

aa1aa2

A

peptide bonds

3-tRNA

G A A

aa3

4-tRNA

G C U

aa4

A C U

U G A

5-tRNA

aa5

Ribosomes move over one codon

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mRNAmRNA

A C A U G U

aa1

aa2

U

primaryprimarystructurestructureof a proteinof a protein

aa3

200-tRNA

aa4

U A G

aa5

C U

aa200

aa199

terminatorterminator or stopor stop codoncodon

TerminationTermination

End Product –The Protein!End Product –The Protein!• The end products of protein

synthesis is a primary structure of a protein

• A sequence of amino acid bonded together by peptide bonds

54aa1

aa2 aa3 aa4aa5

aa200

aa199

Messenger RNA (mRNA)Messenger RNA (mRNA)

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methionine glycine serine isoleucine glycine alanine stopcodon

proteinprotein

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

startcodon

Primary structure of a proteinPrimary structure of a protein

aa1 aa2 aa3 aa4 aa5 aa6

peptide bonds

codon 2 codon 3 codon 4 codon 5 codon 6 codon 7codon 1

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