Types of DNA Damage

. Four bases in DNA (A,T,C,G)
    -->  Most frequent is the loss of an amino group resulting for C being converted to U.
It is due to deletion that mutations in which a section of DNA is lost or deleted. Such could also change a codon to one that encodes a different amino acid and cause a change in the protein being produced.



Mismatches of normal bases during DNA replication.
      --> Loss of ammonia to gain water.
      --> Pyrimidine U is being replaced instead of T after the DNA damage. 

TYPES OF DAMAGES

Due to the presence of UV light, it might cause break in the sugar-phosphate backbone.

There are two types of break:

• Can be limited to one of the two strands (a single-stranded break, SSB) or
• on both strands (a double-stranded break (DSB). 

Two types of breaks in the sugar phosphate backbone can also be caused by ionizing radiation. A single strand break occurs when only one of the sugar phosphate backbones is broken. Single strand breaks are readily repaired using the opposite strand as a template.

Double-strand are difficult to repair, they can cause mutations and cell death. Unrejoined double strand breaks are cytotoxic (they kill cells). Double strand breaks can also result in the loss of DNA fragments which, during the repair process, can cause the joining of non-homologous chromosomes (chromosomes not of the same pair).

When cells are exposed to sunlight, radiant energy can damage the DNA. One of the damage caused by the UV radiation is ultraviolet irradiation causes covalent bond formation between adjacent thymines on the same strand of DNA.

When DNA is damaged in this way, it cannot be replicated or transcribed because when the thymine  and thymine form covalent bond, it will form a thymine dimers and creates a hump.

Nucleotide Excision Repair

Steps taken to repair the damaged DNA:

1. The damage is recognized by one or more protein factors that assemble at the location.
2. The DNA is unwound producing a "bubble". The enzyme system that does this is Transcription Factor IIH, TFIIH, (which also functions in normal transcription).
3. Cuts are made on both the 3' side and the 5' side of the damaged area so the tract containing the damage can be removed.
4. A fresh burst of DNA synthesis — using the intact (opposite) strand as a template — fills in the correct nucleotides. The DNA polymerases responsible are designated polymerase delta and epsilon.
5. A DNA ligase covalently inserts the fresh piece into the backbone.

What causes skin cancer?

UV Radiation

This is the main causes of skin cancer from getting into contact with the sun in a long period of time. This is due to the reason that energy from the sun is actually a form of radiation.  It is also that there is an invisible infra-red radiation that makes sunlight feel hot and hence people would get sunburnt easily when under the sun too long.

UV rays damage DNA,the genetic material that makes up genes and genes control the growth and overall health of skin cells. It is that if the genetic damage is severe,a normal skin cell may begin to grow in the uncontrolled way of cancer cells.

It is also that some people that get skin cancer is due to the reason that hereditary in families and also there is abnormal genes that they inherited from their parents and so they would likely get the same diseases passed down from their parents.

MUTATION

MUTATION is the changing of the structure of a gene.

The factors that caused mutation is:
- DNA fails to copy accurately

Most of the mutations that we think matter to evolution are "naturally-occurring."
For example, when a cell divides, it makes a copy of its DNA — and sometimes the copy is not quite perfect. That small difference from the original DNA sequence is a mutation.

- External influences
Mutations can also be caused by exposure to specific chemicals or radiation. These agents cause the DNA to break down. When the cell repairs the DNA, it might not do a perfect job of the repair and thus, caused mutation.

What are the consequences of skin cancer?

SYMPTOMS:

Basal cell carcinoma: caused by long-term exposure to sunlight

• Shiny bump that is pearly or translucent
• Flat, flesh-colored lesion appearing anywhere on the body

Squamous cell carcinoma:

• Hard, red nodule on face, lips, ears, neck, hands, arms
• Flat lesion with scaly surface

Melanoma:

• Change in color, size, shape or texture of a mole
• Skin lesion with irregular borders
• Enlargement of an existing skin lesion
• Large brown spot with darker speckles
• Hard, dome-shaped bumps anywhere on your body

Characteristics:

• Fair skin
• Spend a lot of time outdoors in work or leisure activities
• History of sunburn
• Family history of skin cancer
• Many moles
• Are over age 40
• Large dark-colored birthmark known as congenital melanocytic nevus
• Pre-cancerous skin lesions, such as actinic keratosis
• HIV (human immunodeficiency virus) -- a risk for Kaposi's sarcoma specifically

Photolyase

          A DNA repair enzyme which recognizes and remove dimers that have formed between pyrimidine nitrogenous bases on the same strand as each other as a result of too much ultra violet rays radiation.

          The enzyme can only do this if visible light is present (absorbs photon with the help of co-factor). 

Mismatch Repair (MMR)

Mismatch Repair (MMR)
Mismatch repair deals with correcting mismatches of the normal bases, that fails to maintain normal base pairing (A•T, C•G)

It can enlist the aid of enzymes involved in both base-excision repair (BER) and nucleotide-excision repair (NER) as well as using enzymes specialized for this function.

• Recognition of a mismatch requires several different proteins 
• Cutting the mismatch out also requires several proteins

Repairing Strand Breaks
Ionizing radiation and certain chemicals can produce both single-strand breaks (SSBs) and double-strand breaks (DSBs) in the DNA backbone.

- Single-Strand Breaks (SSBs)
Breaks in a single strand of the DNA molecule are repaired using the same enzyme systems that are used in Base-Excision Repair (BER).

- Double-Strand Breaks (DSBs)
There are two mechanisms by which the cell attempts to repair a complete break in a DNA molecule.

• Direct joining of the broken ends. This requires proteins that recognize and bind to the exposed ends and bring them together for ligating. They would prefer to see some complementary nucleotides but can proceed without them so this type of joining is also called Nonhomologous End-Joining (NHEJ). 

Answering Problem Statement

Problem Statement 

A 

• Normal cell 
• Contains the normal level of ligase and photolyase = normal level of repair (can be lower than the affecting level) = Shorter time of survival

B 

• Mutated cell, increased production of photolayse 
• More photolayse = Higher rate of repair of cell = Causing the cell to survive longer and reproduce normally 

C

• Mutated cell, lacks in enzyme ligase IV 
• No ligase = DNA replication is not complete as linkage between okazaki fragments = Unable to produce and repair = Shorter time of survival 

Base Excision Repair (BER)

The steps and some key players:

1. Removal of the damaged base (estimated to occur some 20,000 times a day in each cell in our body!) by a DNA glycosylas
2. We have at least 8 genes encoding different DNA glycosylases each enzyme responsible for identifying and removing a specific kind of base damage
3. Removal of its deoxyribose phosphate in the backbone, producing a gap. We have two genes encoding enzymes with this function
4. Replacement with the correct nucleotide. This relies on DNA polymerase beta, one of at least 11 DNA polymerases encoded by our genes
5. Ligation of the break in the strand. Two enzymes are known that can do this; both require ATP to provide the needed energy. 

DNA Ligase IV

What is DNA Ligase IV? 

• DNA ligase is a specific type of enzyme, a ligase that repairs single-stranded discontinuities in double stranded DNA molecules
• In simple words strands that have double-strand break (a break in both complementary strands of DNA).
• DNA ligase is used in gene cloning to join DNA molecules together.
• A single-strand break, is fixed by a different type of DNA ligase using the complementary strand as a template, but still requires DNA ligase to create the final phosphodiester bond  to fully repair the DNA.