Leuture 5 DNA discovery and structure

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71 Terms

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<p>What is the Biological Function</p>

What is the Biological Function

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Gregor Mendel (1822-1884) revealed that….

heredity is the result of discrete units of inheritance.

  • Traits are not blended - can either have mom or Dad traits can be pasted down generation from generation

<p>heredity is the result of discrete units of inheritance.</p><ul><li><p>Traits are not blended - can either have mom or Dad traits can be pasted down generation from generation</p></li></ul>
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Wilhelm Ludvig Johannsen coined the term gene to refer the …

not or particle of inheritance

  • Phenotype - Trait expressed by gene

  • Genotype - collection of genes that code for phenotype

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Archibald Garred

Identifies alkaptonuria as a heritable geneticc disease that follows Mendel’s law

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Alkaptonuria

  • black urine - inborn error of metabolism used of pedigree

<ul><li><p>black urine - inborn error of metabolism used of pedigree</p></li></ul>
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What is the Biochemical basis of hereditary?

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Majority of death resulted from secondary infections of…

Streptococcus pneumoniae

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What are the two strains of streptococcus pneumoniae

  • Rough Colony (R)

  • Smooth Colony (S)

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What is the R strain

benign (lacks a protective capsule, recognized and destroyed by host’s immune system)

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S-strain

Is virulent (polysaccharide capsule prevents detection by host’ immune system)

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<p>Fredirck Griffith (1928) discovered that the ..</p>

Fredirck Griffith (1928) discovered that the ..

dead virulent strain of S. pneumonia (S-strain) could transform the harmless form (R-strain) into the virulent form.

<p>dead virulent strain of S. pneumonia (S-strain) could transform the harmless form (R-strain) into the virulent form.</p>
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Avery, and McCarty and Mcleod discovered that…

R-strains could be transformed with DNA extracts from dead S-strains

<p>R-strains could be transformed with DNA extracts from dead S-strains</p>
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Conclusion

the molecule that carries the heritable information is DNA

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Bacteriophage are?

They consist of two component

  • Class of Viruses that infect bacteria

  • Requires bacterial host for replication

  • DNA Genome

  • Protein Capsid

<ul><li><p>Class of Viruses that infect bacteria</p></li><li><p>Requires bacterial host for replication</p></li></ul><p></p><ul><li><p>DNA Genome</p></li><li><p>Protein Capsid</p></li></ul>
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Bacteriophage life cycle

The genetic information required for viral replication must be contained in either the DNA or the proteins

<p>The genetic information required for viral replication must be contained in either the DNA or the proteins</p>
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Hershey and chase (1952)

Labeled Bacteriophage with radioactive elements

  • Phosphorous of DNA

  • The sulfur of Amino Acids - Cysteine and methionine

  • Traced the transfer of those elements to the infected bacteria

<ul><li><p>Phosphorous of DNA</p></li><li><p>The sulfur of Amino Acids - Cysteine and methionine</p></li></ul><p></p><ul><li><p>Traced the transfer of those elements to the infected bacteria</p></li></ul>
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Hershey and Chase confirmed What?

Experiment DNA and Protein/sulfur put in viruses that allowed to infect E.coil- blender shear off viral heads off bacter- infected bacteria contained 35P not S35

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Nucleotides

A nucleotide consist of a nitrogen-containing base, a five-carbon sugar, and one or more phosphate groups

Carbons of the deoxyribonucleotide (monomer unit of DNA)

<p>A nucleotide consist of a nitrogen-containing base, a five-carbon sugar, and one or more phosphate groups</p><p></p><p>Carbons of the deoxyribonucleotide (monomer unit of DNA)</p>
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1’

Base attached

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2’

Deoxygenated in DNA

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3’

OH - forms phosphodiester bond

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5’

Phosphate group attached

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What are the Nucleotide bases

What are Pyrimidine and Purine bases

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<p>DNA Polymerization</p>

DNA Polymerization

  • Hydrolysis of Phosphor anhydride bond provide energy

  • Creates favorable reaction - high energy → Low energy

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Erwin Chargaff do?

Nucleotide occur in predictable ratios in living things

<p>Nucleotide occur in predictable ratios in living things</p>
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What is Chargaff's Rule?

A = T

G = C

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Discovery of the structure of DNA - Watson, Crick, Wilkins, and Franklin

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Discovery of structure of DNA - Watson, Crick, Franklin, and Wilkins

  • Double helix with Bases pointing inward

  • Complementary base-pairing between purine and pyrimidine explain Chargaff’s rule

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Complementary base-pairing of DNA makes it possible to faithfully replicate of genetic material

  • Each strand serves as a template to make a new double helix - semi-conservative replication.

<ul><li><p>Each strand serves as a template to make a new double helix - semi-conservative replication.</p></li></ul>
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Part 2 - DNA and Chromatin Structure

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DNA Structure backbone is assembled via condensation reactions forming…

Phosphodiester bonds

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Nucleotides are connected 5’ to 3’ and strands are..

one strand and the other…

  • antiparallel

  • One strand runs 5’ to 3’

  • Other runs 3’ to 5’

<ul><li><p>antiparallel</p></li></ul><p></p><ul><li><p>One strand runs 5’ to 3’</p></li><li><p>Other runs 3’ to 5’</p></li></ul>
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DNA Structure is held together by…

Hydrogen bonds between bases

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G to C bonds are… than A to T

Stronger

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Increasing the GC content increases the … of DNA

Stability

<p>Stability</p>
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The DNA Helix has two grooves

  • Major groove - 22 A wide - primary site of sequence specific binding of protein

  • Minor groove - 12 A wide - primary non-specific binding of proteins

<ul><li><p>Major groove - 22 A wide - primary site of sequence specific binding of protein</p></li><li><p>Minor groove - 12 A wide - primary non-specific binding of proteins</p></li></ul>
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Major DNA sequence features (2)

  • Genome

  • Gene

<ul><li><p>Genome</p></li><li><p>Gene</p></li></ul>
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Genome?

The complete DNA sequence of an organism

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Gene

Portion of the genome transcribed to RNA and usually translated into a protein

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Genes are read (transcribed) …..from either strand of the double helix

5’ to 3’

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Replication Origin

Special sequence where the replication of DNA begins

<p>Special sequence where the replication of DNA begins</p>
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Centromere

A special sequence that attaches to mitotic spindle and allows chromosome separation in mitosis

<p>A special sequence that attaches to mitotic spindle and allows chromosome separation in mitosis</p>
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Telomere

Repetitive sequences at the ends of Chromosomes that protect from degradation and/or fusion with other chromosomes

<p>Repetitive sequences at the ends of Chromosomes that protect from degradation and/or fusion with other chromosomes</p>
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The Problem with DNA is that it’s Thin and Extremely long molecule.

  • Each cell in your body has 2 meters of DNA

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How does DNA fit in the cell?

DNA is packed with proteins into a complex called chromatin

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Histone proteins are major elements of…

chromatin

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Histone protein come together in an …. complex which DNA wraps around.

Octomer

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Nucleosome?

The histone + DNA Complex

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Histones proteins are…. charged and attract the …. charged DNA

Positively charged

Negatively charged

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Decondense Chromatin appears like …..

DNA wraps around nucleosome ….times …bp

Beads on a string

1.7 times (147 basepairs)

<p>Beads on a string</p><p></p><p>1.7 times (147 basepairs)</p>
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Another histone protein…. can …

H1 can link histones together and help condense the chromatin fibers

<p>H1 can link histones together and help condense the chromatin fibers</p>
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Chromatin fibers are … into loops by …

Folded

CTFC proteins

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What do CTFC do?

Pull loop through until it reaches a specific sequence

  • Matches Specific DNA Sequences

  • Chromosome loop-forming clamp proteins

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What is the Result of this?

Each DNA molecule has been packaged into a Mitotic chromosome that is 10,000-fold shorter than its fully extended length

  • Fully condense at Meta-phase of cell cycle

<p>Each DNA molecule has been packaged into a Mitotic chromosome that is 10,000-fold shorter than its fully extended length</p><p></p><ul><li><p>Fully condense at Meta-phase of cell cycle</p></li></ul>
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DNA in Eukaryote cells is organized into ..

Chromosomes

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What is a chromosome

Complex of DNA (One continuous helix) and many proteins

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In human chromosomes are paired …

Homologous chromosomes, one from each parent

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Chromosomes take on different conformations through the cell cycle

Interphase, meta phase, interphase

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In interphase, when cell is not dividing,..

different chromosomes reside in distinct territories within the nucleus.

<p>different chromosomes reside in distinct territories within the nucleus.</p>
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Nucleus chromatin is found in two forms

  • Heterochromatin

  • Euchromatin

<ul><li><p>Heterochromatin</p></li><li><p>Euchromatin</p></li></ul>
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Heterochromatin

That is condensed and not transcriptionally active by telomere and centromere.

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Euchromatin

That is loose and transcriptionally active

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<p></p>

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Chromatin conformation and composition is dynamic and modified for specific biological function

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Chromatin remodeling complex (3)

  • Positions nucleosomes

  • Condenses and decondense

  • Requires ATP

<ul><li><p>Positions nucleosomes</p></li><li><p>Condenses and decondense</p></li><li><p>Requires ATP</p></li></ul>
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The Histone proteins have….terminal tails that are…

N-terminal tails that are modified to mark regions of genome for transcriptional activation or silencing

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What are the 5 Levels of DNA

  1. Double helix

  2. Beads on a string - DNA wraps around Histone 1.7 times 147bp creating nucleosome

  3. Chromatin fibers are made with Histone HI

  4. Chromatin fiber loops with CTFC - pull loop through until it reaches a specific sequence

  5. Folded loops are fully condensed at meta-phase of cell cycle

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