The central dogma overview of dna how does dna control the cell
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The “Central Dogma” Overview Of DNA How does DNA control the cell?. Transcription. Translation. DNA. mRNA. proteins. Enzymes Structure Movement Hormones Gas exchange Amino Acid Storage. Replication. So how does DNA “control” the cell?. Transcription. Translation. DNA. mRNA.

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The “Central Dogma” Overview Of DNA How does DNA control the cell?

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The central dogma overview of dna how does dna control the cell

The Central DogmaOverview Of DNAHow does DNA control the cell?

Transcription

Translation

DNA

mRNA

proteins

Enzymes

Structure

Movement

Hormones

Gas exchange

Amino Acid Storage

Replication


So how does dna control the cell

So how does DNA control the cell?

Transcription

Translation

DNA

mRNA

proteins

Enzymes

Structure

Movement

Hormones

Gas exchange

Amino Acid Storage

Replication


Thomas hunt morgan

Thomas Hunt Morgan


Frederick griffith

Frederick Griffith


Oswald avery maclyn mccarty and colin macleod

Oswald Avery, Maclyn McCarty, and Colin MacLeod


Alfred hershey and martha chase

Alfred Hershey and Martha Chase


Erwin chargaff

Erwin Chargaff

  • A = 30.9%

  • T = 29.4%

  • G = 19.9%

  • C = 19.8%


Watson crick and franklin

Watson, Crick, and Franklin


Matthew meselson and franklin stahl

Matthew Meselson and Franklin Stahl


From dna to chromosome

From DNA to Chromosome

chromosome

nucleus

  • A strand of human DNA is about 3 m long

  • How does it fit into all our cells??

  • Supercoiling

cell

Proteins that DNA wraps around

histones

Base pairs

DNA


Details of dna structure

Details of DNA Structure

  • Nucleotides are the monomers of nucleic acids

  • 5 carbon sugar

    • Ribose

    • Deoxyribose

  • Nitrogen Base

    • Adenine

    • Thymine

    • Cytosine

    • Guanine

    • Uracil

  • Phosphate

5 Carbon

5

4

1

2

3

3 Hydroxyl


Details of dna structure1

Details of DNA Structure

5 Carbon

3 Hydroxyl

  • What do you notice about the 5 and 3 ends of the two strands?

  • Theyre ANTIPARALLEL!!

  • Why? For the nucleotide bases to line up

3 Hydroxyl

5 Carbon


Details of dna structure2

Details of DNA Structure

5 Carbon

3 Hydroxyl

  • What holds the nucleotides together?

3 Hydroxyl

5 Carbon


The central dogma overview of dna how does dna control the cell

Details of DNA Structure

  • Nucleotide Bases: Purines and Pyrimidines

    • PURINES

      • Aggies are Pure A and G are Purines which have 2 rings

    • PYRIMIDINES

      • TCU Cheerleaders build Pyramids T and C are Pyrimidines have one ring


Key questions

Key Questions

  • How do 3 m of DNA fit into each of our cells? (be specific!)

  • Why is a DNA molecule considered to have direction and to be anti-parallel?

  • What type of bonds form the sugar-phosphate backbone?

  • What type of bonds hold the nucleotide bases together?

  • From what you know about the bonding between base pairs, which pairs (A-T or G-C) do you think have more breaks and mistakes and why?


Question

Question:

  • How does the structure of DNA ensure the daughter strands will be identical to the parent strand?


Dna replication

DNA Replication

Parent strand

Origin of replication

Daughter strand

Bubble

Replication fork

2 new strands


Dna enzymes

DNA Enzymes

  • Helicase

    • Breaks hydrogen bonds to unwind DNA

  • DNA Polymerase III

    • Adds nucleotides ONLY to the 3 end

    • Nucleoside PPP links to sugar-P backbone

    • Losing 2 Ps provides energy for bonding


The central dogma overview of dna how does dna control the cell

  • Problem: Nucleotides can only be added to the 3 end by DNA Polymerase

  • Solution: Okazaki

  • Leading and Lagging Strands

    • Leading Strand

      • Continuous synthesis

    • Lagging Strand

      • Okazaki fragments

      • Joined by ligase


The central dogma overview of dna how does dna control the cell

3

Remember: DNA polymerase can only add nucleotides to the 3 end, so DNA gets built in the 5 3 direction!

5

Parental DNA

5

Okazaki fragments

3

DNA polymerase

3

Ligase

Leading and lagging have the same origin of replication, but since DNA polymerase can only add on the 3 end, the lagging strand has to start backwards and make little pieces to link together

5

Leading strand

One piece of 5 3

Many little pieces of 5 3 linked together later

Lagging strand


The central dogma overview of dna how does dna control the cell

Test your understandingOn some paper, write A H and decide whether each letter represents the 3 or 5 end of DNA. Then, label the sections (A-B, C-D, etc) as leading or lagging

A-B: Leading

C-D: Lagging

B

C

A

D

5

3

3

5

3

5

E

H

3

5

G

F

F-E: Leading

H-G: Lagging


Priming dna synthesis

Priming DNA Synthesis

  • DNA polymerase can only extend an existing DNA molecule; it cannot start a new one

    • Short RNA primer is built first on parent DNA by primase

    • RNA primer later removed by DNA polymerase I


Priming dna synthesis1

Priming DNA Synthesis

  • Closer look

Primase builds the RNA primer

Replaces RNA nucleotides with DNA

Primase

DNA polymerase


Putting it all together

Putting it all together!

  • http://www.johnkyrk.com/DNAreplication.html


Editing and proofreading dna

Editing and Proofreading DNA

Why do we not always get cancer?

DNA can repair itself!!!

  • Since DNA polymerase III does 1,000 base pairs/second, it makes a lot of errors

  • DNA Polymerase I (only 20 bp/sec) excises mismatched bases, repairs the DNA, and removes the primer

  • DNA polymerase I reduces error from 1 in 10,000 bp to 1 in 100 million bp!!


Problems at the end

Problems at the end

  • Ends of chromosomes are eroded with each replication (dont get fully copied)

  • Telomeres are expendable, non-coding sequences at the ends of the DNA strand

    • short sequence of bases repeated 1000s of times

  • TTAGGG in humans


Telomeres and aging

Telomeres and Aging

telomere

  • In the absence of telomerase, the telomere will become shorter after each cell division. When it reaches a certain length, the cell may cease to divide and die.

telomerase

Extended telomere


Putting it all together1

Putting it ALL together

  • Summarize the roles of the key enzymes

  • Label the diagram showing the steps of DNA replication

  • DNA Structure Questions and Practice


Summary of replication enzymes

Summary of Replication Enzymes

Unzips DNA (breaks H-bonds between nucleotides)

Builds RNA primer in leading strand and Okazaki fragments

Adds DNA nucleotides (20 bp/s); replaces RNA primer with DNA; repairs errors in DNA

Adds DNA nucleotides (1,000 bp/s)

Joins Okazaki fragments (using phosphate groups)


The central dogma overview of dna how does dna control the cell

  • In the diagram below, label the key enzymes and structures in DNA replication. Be sure to label 3 and 5 ends, too!


Protein synthesis

Protein Synthesis

  • How does DNA control the structure and function of the cell?

    it makes proteins!

    • Structure: collagen, elastin, keratin

    • Enzymes: catalase, amylase, sucrase, etc

    • Hormones: insulin, glucagon, etc

    • Amino acid storage: albumin, ovalbumin, etc


The central dogma overview of dna

The Central DogmaOverview Of DNA

Transcription

Translation

DNA

mRNA

proteins

Enzymes

Structure

Movement

Hormones

Gas exchange

Amino Acid Storage

Replication


The main things for dna transcription and translation

The Main Things forDNA Transcription and Translation


Let s model it

Lets model it


Protein synthesis1

Protein Synthesis!

  • Transcription

  • http://www.johnkyrk.com/DNAtranscription.html

  • Translation

  • http://www.johnkyrk.com/DNAtranslation.html


Notas from gene to protein

Notas From Gene to Protein

Metabolism teaches us about genes

  • Metabolic defects caused by non-functional enzyme

  • Studying metabolic diseases suggested that genes specified proteins

    • PKY

    • Alkaptonuria (black urine)

  • Genes dictate the phenotype


The central dogma overview of dna how does dna control the cell

1 gene 1 enzyme hypothesis

  • Beadle and Tatum 1941


The central dogma overview of dna how does dna control the cell

1 gene 1 enzyme hypothesis

  • Beadle and Tatum 1941

    • Compared different nutritional mutants of bread mold, Neurospora

    • Created mutations by X-ray treatments X-rays break DNA)

    • Wild type grows on minimal media (sugar)

    • Mutants require different amino acids because each mutant lacks a certain enzyme needed to produce a certain amino acid

    • Conclusion: Broken gene = non-functional enzyme

  • Problems with:

    • One gene one enzyme

      • not all proteins are enzymes, and theyre coded by genes too

    • One gene one protein

      • many proteins consist of several polypeptide, and each polypeptide has its own gene

  • One gene one polypeptide?


Defining a gene

Defining a gene

  • Defining a gene is problematic because small genes can be difficult to detect, one gene can code for several protein products, some genes code only for RNA, two genes can overlap, and there are many other complications. Elizabeth Pennisi, Science 2003

  • How would YOU define a gene in your own words?


The central dogma

The Central Dogma

Transcription

Translation

DNA

mRNA

Protein

Reverse Transcription

Replication


From nucleus to cytoplasm

From nucleus to cytoplasm

  • Where are the genes?

    in DNA on chromosomes in the nucleus

  • Where are proteins synthesized?

    on ribosomes (free or on the ER) in the cytoplasm

  • How does the information get from the nucleus to the cytoplasm?

    mRNA is made in the nucleus and can travel into the cytoplasm to the ribosomes


The central dogma overview of dna how does dna control the cell

deoxyribose

ribose

A-T, C-G

T-A, A-U, C-G

Double

Single


Transcription basics

Transcription Basics

  • Initiation

    • RNA polymerase binds to promoter sequence on DNA

      • where to start reading = Promoter (initiation site)

      • which strand to read = template strand

      • direction on DNA = reads 35 builds 5 3

  • Elongation

    • RNA polymerase unwinds DNA ~20 bp at a time

    • Reads DNA 3 5

    • Builds RNA 5 3

    • No proofreading, about 1 error/105 bases

    • Many copies, short life, no problem

  • Termination

    • RNA polymerase stops at termination sequence

    • mRNA leaves nucleus through pores


  • Transcription

    Transcription


    Rna processing or editing

    RNA Processing or Editing

    • 5 cap

      • protection

      • targets mRNA for ribosome

    • Poly-A tail

      • protection

      • leads mRNA out of nucleus

    • Spliceosome

      • composed of snRNPs (small nuclear ribonucleoproteins)

      • introns intervening, interrupting = removed by spliceosome

      • exons expressed


    Sliceosome

    Sliceosome


    Putting it together transcription to translation

    Putting it Together Transcription to Translation

    • How does mRNA code for proteins?

    • How can you code for 20 aa with only 4 nucleotide bases (A, U, G, C)?

    • How can an alphabet of 4 letters (nucleotides) translate into an alphabet of 20 letters (aa)?!


    Breaking the code

    Breaking the code

    • Nirenberg and Matthaei

    • Determined 1st codon amino acid match

      • UUU coded for phenylalanine

    • Created artificial poly(U) mRNA

    • Added mRNA to test tube of ribosomes and nucleotides

      • mRNA synthesized a single amino acid polypeptide chain: phe-phe-phe-phe-phe-phe


    The central dogma overview of dna how does dna control the cell

    DNA

    Gene 1

    3

    5

    DNA

    Transcription

    mRNA

    5

    3

    codon

    Translation

    Protein

    Amino acids


    The code

    The CODE!!

    • For ALL life!! (yes, even prokaryotes)

      • Strongest support for common origin for all life

    • Code is redundant

      • Several codons for each amino acid

    • Start codon: AUG = methionine

    • Stop codons: UGA, UAA, UAG


    Translation

    Translation

    • Ribosome reads mRNA in codons

    • tRNA brings in correct amino acid

    • tRNA matches codon of mRNA = anticodon

    • Amino acids assembled into polypeptide chain


    Trna structure

    tRNA Structure

    • clover leaf structure

      • anticodon on clover leaf end

      • amino acid on 3 end

      • anticodon written 3 5 to match codons which are 5 3


    Aminoacyl trna synthetase

    AminoacyltRNAsynthetase

    • enzyme which bonds amino acid to tRNA

      • endergonic reaction (does it require energy?)

      • ATP AMP (how many phosphates do we use?)

      • Energy stored in tRNA-aa bond

        • Unstable


    Ribosomes

    Ribosomes

    • Facilitate coupling of tRNA anticodon to mRNA codon

      • Organelle or enzyme?

    • Structure

      • Ribosomal RNA and proteins

      • 2 subunits: large and small

      • A site (aminoacyl-tRNA site)

        • Holds tRNA carrying next amino acid to be added to chain

      • P site (peptidyl-tRNA site)

        • Holds tRNA carrying growing polypeptide chain

      • E site (exit site)

        • Discharged tRNA leaves ribosome from exit site


    Building a polypeptide

    Building a Polypeptide

    • Initiation

      • Brings together mRNA, ribosome subunits, proteins and initiator tRNA

  • Elongation

  • Termination

    • Release polypeptide

    • release protein bonds to A site

    • Bonds water molecule to polypeptide chain


  • Polyribosomes

    Polyribosomes

    • Many ribosomes read single mRNA simultaneously making many copies of a protein!


    Protein targeting

    Protein Targeting

    Signal polypeptide

    • ~20 aa at the beginning of the polypeptide

    • Recognized by SRPs (signal recognition particles)

    • SRP brings polypeptide and ribosome to ER so that polypeptide is secreted into the ER as its built3.

  • Destinations other signal polypeptides used to target

    • Secretion

    • Nucleus

    • Mitochondria

    • Chloroplasts

    • Cell membrane

    • Cytoplasm


  • The central dogma overview of dna how does dna control the cell

    Comparing!


    Mutations

    Mutations

    • Point Mutations

      • 1 base pair change

      • Base-pair substitution

        • Silent mutation: no amino acid change because of redundancy in code

        • Missense: change amino acid

    • Nonsense: change to stop


    Mutations1

    Mutations

    • Insertions adding base(s)

    • Deletions losing base(s)

    • BOTH cause frameshift


    Gene regulation

    Gene Regulation

    • In a nutshell


    Prokaryotes regulate transcription through operons

    Prokaryotes regulate transcription through operons.

    Area where RNA Polymerase binds

    Area where repressor can bind to stop binding of RNA polymerase

    Segment of DNA containing several genes, a promoter, and an operator

    Regulatory gene = codes for repressor; gene is upstream/downstream from operator


    2 kinds of feedback

    2 Kinds of Feedback


    Prokaryotes regulate transcription through operons1

    Prokaryotes regulate transcription through operons.

    Area where RNA Polymerase binds

    Area where repressor can bind to stop binding of RNA polymerase

    Segment of DNA containing several genes, promoter, and operator

    Regulatory gene = codes for repressor; gene is upstream/downstream from operator

    Too much product, stop; not enough, keep going!!

    Break it down if youve got it!


    2 examples of negative feedback

    2 Examples of Negative Feedback


    Prokaryotes regulate transcription through operons2

    Area where RNA Polymerase binds

    Area where repressor can bind to stop binding of RNA polymerase

    Prokaryotes regulate transcription through operons.

    Segment of DNA containing several genes, promoter, and operator

    Regulatory gene = codes for repressor; gene is upstream/downstream from operator

    Too much product, stop; not enough, keep going!!

    Break it down if youve got it!

    • Default on because repressor not bound

    • Product binds to repressor to activate and turn off transcription

    • Usually anabolic pathways (ex: trp)


    Prokaryotes regulate transcription through operons3

    Area where RNA Polymerase binds

    Area where repressor can bind to stop binding of RNA polymerase

    Prokaryotes regulate transcription through operons.

    Segment of DNA containing several genes, promoter, and operator

    Regulatory gene = codes for repressor; gene is upstream/downstream from operator

    Too much product, stop; not enough, keep going!!

    Break it down if youve got it!

    • Default on because repressor not bound

    • Product binds to repressor to activate and turn off transcription

    • Usually anabolic pathways (ex: trp)

    • Default off because repressor bound

    • Product binds to repressor to inactivate and release the repressor and turn on transcription

    • Usually catabolic pathways (ex: lac)


    Prokaryotes regulate transcription through operons4

    Area where RNA Polymerase binds

    Area where repressor can bind to stop binding of RNA polymerase

    Prokaryotes regulate transcription through operons.

    Segment of DNA containing several genes, promoter, and operator

    Regulatory gene = codes for repressor; gene is upstream/downstream from operator

    Too much product, stop; not enough, keep going!!

    Break it down if youve got it!

    • Presence of activator turns on

    • Ex: lac with lactose and no glucose

    • Default on because repressor not bound

    • Product binds to repressor to activate and turn off transcription

    • Usually anabolic pathways (ex: trp)

    • Default off because repressor bound

    • Product binds to repressor to inactivate and release the repressor and turn on transcription

    • Usually catabolic pathways (ex: lac)


    Eukaryotes regulate gene expression pre transcription during transcription and post transcription

    Eukaryotes regulate gene expression pre-transcription, during transcription, and post-transcription.

    • Histone acetylation

    • Acetylated = less bound = easier access

    • DNA methylation

    • methylated = more bound = less access

    • Controls access of RNA polymerase to promoter


    Eukaryotes regulate gene expression pre transcription during transcription and post transcription1

    Eukaryotes regulate gene expression pre-transcription, during transcription, and post-transcription.

    • Histone acetylation

    • Acetylated = less bound = easier access

    • DNA methylation

    • methylated = more bound = less access

    • Controls access of RNA polymerase to promoter

    • Transcription Factors = proteins that help RNA poly binding at promoter

    • Activation sites and enhancer proteins = also aid in RNA poly binding; 1000s of bp away

    • Aids in RNA polymerase binding


    Eukaryotes regulate gene expression pre transcription during transcription and post transcription2

    Eukaryotes regulate gene expression pre-transcription, during transcription, and post-transcription.

    • Histone acetylation

    • Acetylated = less bound = easier access

    • DNA methylation

    • methylated = more bound = less access

    • Controls access of RNA polymerase to promoter

    • Transcription Factors = proteins that help RNA poly binding at promoter

    • Activation sites and enhancer proteins = also aid in RNA poly binding; 1000s of bp away

    • Aids in RNA polymerase binding

    • Poly-A tail

    • 5 cap

    • Alternate splicing = different combos of exons are expressed (some can be removed)

    • Essential in making antibodies

    • Alters mRNA transcript


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