DNA Structure & Function (Outline)faculty.sdmiramar.edu/bhaidar/bhaidar 210A web uploads/Bio...

DNA Structure amp Function (Outline)1 Historical perspective (DNA as the genetic material)

bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rulebull DNA structure

2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA

3 DNA replication models4 Mechanism of DNA replication steps and molecular

machinery5 Replication and the end of linear chromosomes-

Molecular basis for aging6 Fidelity of DNA replication

By definition the genetic material of must

bull be replicated DNA Replication

bull direct the cell functions by providing information for production of proteins

Flow of the genetic information(Gene Expression)

Current Connections to

DNA structure and replication

Why are we mortal with a limited life span

DNA as the Genetic MaterialTime-line

1850rsquos Mendel 1870-1890 Microsocopy Mitosis and Meiosis1902 Chromosome basis of inheritance

(Thomas H Morgan)20th century Work with bacteria and viruses

1928 Fredrick Griffith ExperimentsConcept of transformation (using Bacteria that cause pneumonia in mammals)

1944 Avery McCarty and MacLeodThe transforming material is DNAldquoDNA is the genetic materialrdquo

1952 Hershey and ChaseDNA is the genetic material in viruses that infect bacteria

Griffith- Phenomenon of Transformation a change in genotype (genetic makeup) by a foreign substance that

changes the phenotype (observed properties) of the cell

History of DNAAvery MacLeod and McCarty 1944

- DNA is the transforming material

(Can convert Type R bacteria into S)

bull A phage is a virus that infects bacteria and is made of DNA and protein

bull Alfred Hershey and Martha Chase- the genetic material of the phage T2 is DNA

httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml

DNA Structure

Prior to the 1950s DNA is a polymer of nucleotides consisting ofbull a nitrogenous base bull a sugarbull a phosphate group

Polarity and anti-parallel nature of the two DNA strands (5rsquo and 3rsquo ends)

DNA Structure amp Function1 Historical perspective (DNA as the genetic material)

bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure





Biochemical analysis of DNA Base-pairing rule

1947 Erwin Chargaff analysis of DNA from different species A = T amp C = G

Human DNA A = 309T = 294C = 199G = 198

Base-pairing in DNA

Maurice Wilkins and Rosalind Franklin- X-ray crystallography Polynucleotide Helix

Franklinrsquos X-ray diffractionPhotograph of DNA

(a) Rosalind Franklin (b)

Structural Model of DNA

Watson and Crick deduced that DNA was a double-stranded helix Through observations of the X-ray crystallographic images of DNA

Watson and Crick - Specificity of pairing is dictated by the structure of

the bases

Example

Three models for DNA replicationConservative modelSemi-conservative modelDispersive model

Bacteriacultured in mediumcontaining15N

DNA samplecentrifugedafter 20 min(after firstreplication)

DNA samplecentrifugedafter 40 min(after secondreplication)

Bacteriatransferred tomediumcontaining14N

Lessdense

Moredense

Meselson-Stahl experiment


The Basic concept of DNA replication

Each strand of DNA act as a template for synthesis of new complementary strands







Molecular Mechanism of DNA Replication

Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)

Direction of replication of new strands 5rsquo-----3rsquo

How nucleotides are added in DNA replicationhttphigheredmcgraw-

hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication

The new strand always starts with the 5rsquo end the template starts with the 3rsquo end

DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand

Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)

Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end

Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-

TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of

DNA polymerase and other proof reading systems

Origin of Replication

TP 7-14

Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein

Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional







Lagging strand

5prime

3prime

Last fragment

RNA primer

Previous fragment

Primer removed butcannot be replacedwith DNA becauseno 3prime end available

for DNA polymerase

5prime

3prime

Removal of primers andreplacement with DNAwhere a 3prime end is available

Second roundof replication

5prime3prime5prime

3primeFurther roundsof replication

New leading strandNew leading strand

Shorter and shorterdaughter molecules

Replicating the Ends of linear DNA Molecules

Mechanism of DNA replication causes telomeres to get shorter with each round of replication

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Q Why are we mortal with a limited life span

A Our cells have a limited life span ( of cell divisions)

Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)

httpswwwyoutubecomwatchv=AJNoTmWsE0s

httpswwwyoutubecomwatchv=vtXrehpCPEE

Ends of linear chromosomes have special DNA sequences and are known as telomeres

added by an enzyme known as telomerase after DNA replication is completed

1

Figure 23

Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone

marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell

divisionbull After about 50 divisions shortened telomeres signal the

cell to stop dividing

Fidelity of DNA replication amp maintaining DNA integrity

Maintained by

1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov

DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48

Genetic Integrity and Diversity

bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on

bull Few errors of DNA replication are not corrected

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Current Connections to DNA structure and replication

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History of DNA

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Base-pairing in DNA

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Summary of DNA Replication

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By definition the genetic material of must

bull be replicated DNA Replication

bull direct the cell functions by providing information for production of proteins

Flow of the genetic information(Gene Expression)


















DNA Structure











Human DNA A = 309T = 294C = 199G = 198

Base-pairing in DNA







the bases

Example






Lessdense

Moredense
























TP 7-14









Lagging strand

5prime

3prime

Last fragment

RNA primer

Previous fragment


for DNA polymerase

5prime

3prime



5prime3prime5prime
















1

Figure 23






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History of DNA

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Base-pairing in DNA

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DNA Structure











Human DNA A = 309T = 294C = 199G = 198

Base-pairing in DNA







the bases

Example






Lessdense

Moredense
























TP 7-14









Lagging strand

5prime

3prime

Last fragment

RNA primer

Previous fragment


for DNA polymerase

5prime

3prime



5prime3prime5prime
















1

Figure 23






Maintained by






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History of DNA

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Base-pairing in DNA

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Human DNA A = 309T = 294C = 199G = 198

Base-pairing in DNA







the bases

Example






Lessdense

Moredense
























TP 7-14









Lagging strand

5prime

3prime

Last fragment

RNA primer

Previous fragment


for DNA polymerase

5prime

3prime



5prime3prime5prime
















1

Figure 23






Maintained by






Slide Number 1

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History of DNA

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Base-pairing in DNA

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Base-pairing in DNA







the bases

Example






Lessdense

Moredense
























TP 7-14









Lagging strand

5prime

3prime

Last fragment

RNA primer

Previous fragment


for DNA polymerase

5prime

3prime



5prime3prime5prime
















1

Figure 23






Maintained by






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History of DNA

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Base-pairing in DNA

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the bases

Example






Lessdense

Moredense
























TP 7-14









Lagging strand

5prime

3prime

Last fragment

RNA primer

Previous fragment


for DNA polymerase

5prime

3prime



5prime3prime5prime
















1

Figure 23






Maintained by






Slide Number 1

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History of DNA

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Base-pairing in DNA

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Lessdense

Moredense
























TP 7-14









Lagging strand

5prime

3prime

Last fragment

RNA primer

Previous fragment


for DNA polymerase

5prime

3prime



5prime3prime5prime
















1

Figure 23






Maintained by






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History of DNA

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Base-pairing in DNA

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TP 7-14









Lagging strand

5prime

3prime

Last fragment

RNA primer

Previous fragment


for DNA polymerase

5prime

3prime



5prime3prime5prime
















1

Figure 23






Maintained by






Slide Number 1

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History of DNA

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Base-pairing in DNA

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Lagging strand

5prime

3prime

Last fragment

RNA primer

Previous fragment


for DNA polymerase

5prime

3prime



5prime3prime5prime
















1

Figure 23






Maintained by






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History of DNA

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Base-pairing in DNA

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Base-pairing in DNA

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History of DNA

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DNA Structure & Function (Outline)faculty.sdmiramar.edu/bhaidar/bhaidar 210A web uploads/Bio...

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