DNA: The Molecular Basis of Inheritance

Building a Structural Building a Structural Model of DNAModel of DNA

• After most biologists became convinced that DNA was the genetic material of life, the next challenge was to determine its structure.

• Rosalind Franklin produced a picture of the DNA molecule by using a technique called X-ray crystallography Franklin produced a picture of the DNA molecule using this technique

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Franklin’s X-ray diffractionphotograph of DNA

Rosalind Franklin

• Based on the images, two other scientists named Watson and Crick were able to determine that DNA molecules took a double helix shape.

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5 end

3 end

5 end

3 end

Space-filling modelPartial chemical structure

Hydrogen bond

Key features of DNA structure

0.34 nm

3.4 nm

1 nm

Sugar–phosphatebackbone

5 end

Nitrogenousbases

Thymine (T)

Adenine (A)

Cytosine (C)

DNA nucleotidePhosphate

3 endGuanine (G)

Sugar (deoxyribose)

• Watson and Crick built models of a double helix to match to the X-rays and chemistry of DNAo The side strands, or “backbones” of the DNA

molecule are made of a sugar (deoxyribose) paired with a phosphate.

o The deoxyribose backbones are joined together by a series of molecules called nitrogenous bases.

Nitrogenous BasesNitrogenous Bases• There are two types of nitrogenous bases:

o Purines• Much wider• Include adenine and guanine

o Pyramidines• Much narrower• Include cytosine and thymine

• Watson and Crick reasoned that the pairing was more specific – o Adenine paired only

with Thymineo Guanine paired only

with Cytosine

Base Pairing to a Base Pairing to a Template StrandTemplate Strand

• DNA is a double-helix molecule made of two intertwining strands.

• The two strands of DNA are complementary, meaning each has a set of bases that corresponds with the other.

• In DNA replication, the molecule is be separated into its two strands.o Two new strands can be made from these

templates, duplicating the molecule.

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The parent molecule has two complementary strands of DNA. Each base is paired by hydrogen bonding with its specific partner, A with T and G with C.

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The parent molecule has two complementary strands of DNA. Each base is paired by hydrogen bonding with its specific partner, A with T and G with C.

The first step in replication is separation of the two DNA strands.

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The parent molecule has two complementary strands of DNA. Each base is paired by hydrogen bonding with its specific partner, A with T and G with C.

The first step in replication is separation of the two DNA strands.

Each parental strand now serves as a template that determines the order of nucleotides along a new, complementary strand.

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The parent molecule has two complementary strands of DNA. Each base is paired by hydrogen bonding with its specific partner, A with T and G with C.

The first step in replication is separation of the two DNA strands.

Each parental strand now serves as a template that determines the order of nucleotides along a new, complementary strand.

The nucleotides are connected to form the sugar-phosphate back-bones of the new strands. Each “daughter” DNA molecule consists of one parental strand and one new strand.

Elongating the DNA Elongating the DNA StrandStrand

• Enzymes called DNA polymerases catalyze the elongation of new DNA.

• The rate of elongation is about 500 nucleotides per second in bacteria and 50 per second in human cells.

Proofreading and Proofreading and Repairing DNARepairing DNA

• DNA polymerases also proofread newly made DNA, replacing any incorrect nucleotides.

• Two types of repair:o In mismatch repair, the enzymes replace

incorrect bases with the correct ones.o In nucleotide excision repair, enzymes cut out

and replace entire stretches of DNA that are damaged.

Replicating the Ends Replicating the Ends of DNA Moleculesof DNA Molecules

• DNA polymerase has one significant limitation.• The enzyme has no way to complete one of

the ends.o Every time the DNA is copied, it becomes a little

shorter.

• Cells will divide countless times over the lifespan of an organism. How can DNA be protected, given this limitation?

• Eukaryotic chromosomal DNA molecules have at their ends repeating nucleotide sequences called telomeres.o Telomeres are DNA, but do not actually encode

for any traits.o Telomeres do not prevent the shortening of DNA

molecules, but they postpone it.

• Eventually, the telomeres are worn down and essential genes begin to be lost from the chromosomes.o This is one of the hypothesized

causes of aging.

• An enzyme called telomerase catalyzes the lengthening of telomeres in stem cells.o This enzyme cannot be produced

indefinitely due to an increasing risk of the cell growing uncontrollably (cancer)