DNA Structure and Replication

Genetics

DNA• Can replicate• Is the hereditary

material• Controls cellular

activities by coding for and controlling protein synthesis

Long Road to Discovery

• Griffith observed transformation

• DNA passed from a harmful bacteria into a harmless one, and the new bacteria killed mice in the experiment

Transformation

DNA

• Hershey and Chase confirmed that DNA, and not protein, was the hereditary material

• Labeled viruses and watched what part entered the cell

• The DNA went in, the protein coat stayed out

Deciphering the Structure

• Watson and Crick proposed the final model

• They used the research of many others.

• Levene identified the three parts: a sugar, a nitrogen containing base, and a phosphorous containing part. And that they were always present in equal numbers. Four different bases were recognized.

Deciphering the Structure

• Chargaff showed that equal numbers of the bases adenine and thymine were always present; and that guanine and cytosine were always present in equal numbers.

• Wilkins and Franklin X rayed DNA and revealed a pattern of repeating building blocks.

Deciphering the Structure

• From all of that research, Watson and Crick put together the double helix model.

Deciphering the Structure

• Each repeating unit is a nucleotide.

• The sugar is deoxyribose, and together with phosphate, makes up the sides of the DNA ladder

• The bases make up the rungs

Nucleotide

Deciphering the Structure

• Hydrogen bonds hold the bases together

• Two strands of DNA are joined in the middle by the bases, and then the whole structure twists to become a helix.

Structure of DNA• Antiparallel: the sides of

the ladder run in opposing directions, as if one strand was upside down.

• Each carbon on the deoxyribose sugar is numbered; one strand runs in the 5’ to 3’ direction, the other in the 3’ to 5’ direction. Page 221

The DNA wraps around the histones; the combination of DNA and a histone is a nucleosome

DNA codes for Proteins

• The sequence of the bases: adenine, thymine, cytosine, and guanine determines the order of amino acids in a protein chain.

DNA Replication

• DNA unzips using an enzyme called helicase

• Each strand makes a new side

• This is semiconservative; each new molecule of DNA has one old strand and one new.

Semiconservative

Old strand

New strand

Replication

• Can be done in the lab to just certain sections or fragments of DNA

• Requires a PRIMER, a short segment of nucleotides recognized as a START tag by DNA polymerases

• Primers are on either end of the segment you want to copy

Replication

• Nucleotides can only be added to the 3’ end of the sugar

• Nucleotides can only be added in the 5’ to 3’ direction; the 5’ to 3’ direction refers to the NEW strand being added

• This is easy on one side, but the other strand is 3’ to 5’ (antiparallel)

Antiparallel structure

Replication

• The 5’ to 3’ side must be replicated in short fragments.

• It unzips, and then fragments are added by going up toward the fork and working back down.

• Discontinuous; has a leading strand and a lagging strand

Replication

Replication

• Enzymes are involved• DNA polymerase

attaches short stretches of nucleotides to the template

• DNA ligases connect fragments to make a continuous strand

DNA Repair

• Replication is very accurate—only about one in a million base pairs has a mistake

• Some genes produce repair enzymes

• Discovered when fungi exposed to UV radiation was repaired by being in light

Types of damage and the fix

• Ultraviolet radiation damages DNA

• Causes the formation of an extra bond between two bases on the same strand

• Most frequently happens to thymines

Types of damage and the fix

• This thymine dimer causes a kink in the strand

• Enzymes called photolyases use light to detect and break the extra bond

• This type of repair is called photoreactivation

Types of damage and the fix• Another way to fix

ultraviolet radiation damage is by excision repair

• The dimer is cut out by a nuclease enzyme and is replaced with completely new nucleotides

Types of damage and the fix

• A third type of repair is mismatch repair

• Enzymes proofread• Look for areas where

the bases are not aligned properly, as if the strand slipped

• Most common in repeating sequences

Types of damage and the fix

• Disorders can occur when mutations occur in the repair genes or there are problems in the repair enzymes

• Conditions such as AT, Bloom syndrome, and Hereditary nonpolyposis colon cancer