DNA

DNA

Deoxyribonucleic acid is the genetic material that encodes all the traits that make up a species and is transmitted from one generation to the next. It consists of sugar (deoxyribose) a nitrogenous base and a phosphate group. One unit is a nucleotide. Adenine and Guanine are purines, and Thymine and Cytosine are pyrimidines. A and T appear 30% of the time and G and C appear 20% of the time. DNA goes from 5’ to 3’ end in a double helix

Inheritance

The process by which DNA is passed down from one generation to the next.

Nucleotide

The basic unit of DNA, consisting of a sugar (deoxyribose), a nitrogenous base, and a phosphate group.

Purines

Adenine and Guanine, nitrogenous bases that are part of DNA and pair with specific pyrimidines.

Pyrimidines

Thymine and Cytosine, nitrogenous bases that are part of DNA and pair with specific purines.

DNA replication: Semiconservative Model

The model of DNA replication is where the two strands of DNA separate and each serves as a template for the synthesis of a new complementary strand. This creates 2 new DNA with each DNA containing 1 strand of the original.

Rosalind Franklin

Scientist who contributed to the discovery of the alpha helix structure of DNA.

James and Francis Crick

Scientists who received the Nobel Prize for the discovery of DNA replication.

Helicase

Enzyme that unwinds the DNA molecule during replication.

Topoisomerase

Enzyme that relieves strain in the DNA molecule during replication.

Primase

Enzyme that adds RNA primers to initiate DNA replication.

DNA polymerase 3

Enzyme that adds nucleotides to both strands of DNA during replication. Adds 50 nucleotides per second

DNA polymerase 1

Enzyme that converts RNA primers to DNA on both strands of DNA during replication.

Ligase

Enzyme that joins up all Okazaki fragments during replication.

Okazaki Fragments

Short segments of DNA that are synthesized on the lagging strand during replication.

Telomere

A region of repetitive DNA sequence at the ends of a chromosome that helps maintain chromosomal stability and prevent chromosomal degradation. Each time a cell divides the telomere become slightly shorter

Telomerase

An enzyme that extends the telomere region of DNA, preventing it from getting shorter during replication. it is called the cell immortalizing enzyme. The highest levels of the enzyme are found in gametes and newborn babies. Enzyme levels decline with age but cancer cells have higher levels. Telomere regions are long in children compared to adults and longer in cancer cells

Mismatch repair

The process by which DNA polymerase proofreads and corrects errors in nucleotides during replication. The mismatched nucleotides and their neighbours are removed and replaced with the correct nucleotides by DNA polymerase. THen DNA ligase seals the gap in the DNA backbone

Excision repair

The process by which damaged DNA is cut out and replaced with correct nucleotides. The nuclease enzymes cuts the damage DNA strand at 2 points

Ligation

The process by which DNA ligase seals the remaining nick in the DNA backbone after repair.

DNA Replication Process

1. 2 strands unwind from Helicase

2. A single-stranded binding protein makes sure that DNA stays apart long enough to replicate. Topoisomerase straightens the strands to relieve pressure

3. A Primer (5-10 RNA nucleotides) is added at each origin of the replication site to create a 3’ end. There are hundreds of origins of replication sites causing “bubbles to form”

4. DNA Polymerase 3 binds to the primer at the 3’ end and adds nucleotides in the 5’ to 3’ direction (template strand needs to be 3’ to 5’)

5. For the lagging strand, the DNA polymerase 3 begin" “downstream” from the point of origin. Primase will continually add primers as DNA unzips to allow for DNA polymerase 3 to add nucleotides.

6. DNA polymerase 1 replaces the primers (RNA molecules) with DNA nucleotides. There are multiple primers to replace in the lagging strend and just one primer in the leading strand.

7. When primers are replace by the DNA polymerase there are gaps in between. These are Okazaki fragments. These are joined together by DNA ligase

End Replication Problem

On the last primer site on the lagging strand, DNA polymerase 1 cannot replace it with DNA nucleotides as there is no 3’ site available for the enzyme to attach. As a result, the DNA molecule gets shorter each cycle reducing the length of the DNA molecule which can result in cell death

Fix to the End Replication Problem

Telomerase enzyme has RNA strands that complement the 3’ overhang at the end of the chromosome and the RNA template in the enzyme is used to synthesize the complementary strand by DNA Polymerase 3. The telomerase then shifts down and Primase and DNA polymerase synthesize the complementary strand (lagging strand)

Correction of Errors and DNA Damage

The high rate of nucleotide addition can cause errors in the nucleotides that are added. About 1 in 10,000 bases are incorrect e.g. adding A to G instead A to T. The errors can give rise to mutation and can result in cancer. The cell checks for errors by the DNA polymerase which proof-reads the DNA. It reduces the error rate to 1 in 10 billion

Basic DNA Repair Mechanisms

Thymine dimer distorts the DNA, and the nuclease enzyme cuts the damaged DNA strand at two points. Repair synthesis by DNA polymerase 3 fills the gp and DNA ligase seals the remaining nick in the backbone.

Cause of DNA damage

DNA can be damaged by exposure of cells to UV light, X-rays, cigarette smoke, mutagenic agents