Chapter 14 Blog: Mutation, DNA Repair, and Cancer

Summary of Chapter:

Introduction:

•      A mutation is a heritable change in the genetic material of an organism.
• DNA's base sequence is changed permanently.
• They can be good or bad
• bad/random ones cause changes that are disruptive
• good ones enhance the function; good for evolution and adaptation
• DNA repair systems can reverse DNA damage before a permanent mutation occurs.

Section 14.1:

• Gene mutations are changes in DNA structure.
• This change will alter a particular gene.
• There are different kinds of mutations.
• point mutations only affect a single base pair.
• It has many variations.
• A silent base substitution causes no change.
• A missense base substitution changes one amino acid.
• A nonsense base substitution causes it to become a stop codon.
• An addition or deletion of a single base is called a frameshift, and it produces a different amino acid sequence.
• Mutations can be spontaneous or induced 
• Spontaneous mutations result from abnormalities in biological processes
• Examples: Errors in DNA replication, toxic metabolic products, changes in nucleotide structure, transposons
• Induced mutations are caused by environmental agents that enter the cell and alter the structure of DNA. 
• Agents that cause mutations are called mutagens.
• Chemical agents such as cigarrette smoke
• Physical agents such as UV light and X-rays

Section 14.2: DNA Repair

• Cells contain several DNA systems that can fix different types of DNA alterations

  - each repair system has more than one protein – repair mechanism

  - requires two coordinated events:

- one or more proteins detect something wrong with the DNA

- the abnormality is then repaired

- sometimes it might be directly repaired (direct repair – an enzyme removes the mistake, restoring the DNA back to normal)

• Nucleotide excision repair (NER) – a region that has several nucleotides in the damaged strand of DNA is removed. The rest is used as a template for resynthesis

  - can fix several different kinds of DNA damage (UV damage, chemically modified bases, missing bases, etc)

  - found in prokaryotes and eukaryotes

Section 14.3: Cancer

• Cancer is a disease that revolves around uncontrollable cell division. Cancer is the second leading cause of death in humans (second to heart disease). Overall, one in four Americans will die from it.

  - can be easier to develop based on genetics - is usually an acquired condition that occurs later in life

  - Most human cancers are related to carcinogens - substances that increase the chances that cancer will develop (UV light, cigarette smoke)

- promote genetic changes in somatic cells

- leads to effects on gene expression, effects cell division

• cancer devolpment is a multistep process

  - originates as one cell

  - mutates and grows abnormally

  - the abundance of cells causes a tumor to form

  - some tumors do not become cancerous, some do (malignant)

• cancerous tumors invade healthy tissues and can spread to the bloodstream

  - this process is called metastasis

• malignant tumors cause death if untreated

• a mutant gene that becomes overactive due to mutation and contributes to cell growth is called an oncogene

  - keep cell division turned on by keeping the cell division signaling pathway in a permanent “on” position

  - proto-oncogene – normal gene that can become an oncogene if mutated

• tumor-suppresor genes have a protein that can prevent cancer

  - missing chromosomes can contribute to the failure of these genes

• many types of cancer are caused by viruses that mutate genes

• carcinomas – cancer of the epithelial cells

Stuff:

PubMed Article: Maternal and fetal exposure to four carcinogenic environmental metals.

http://www.ncbi.nlm.nih.gov/pubmed/21315244

A test was done with exposing pregnant women to four metals: arsenic, beryllium, cadmium, and nickel. These metals are carcinogens, which are discussed in section 14.3. Scientists found that while the concentrations were lower, the carcinogens could also be found in the umbilical cord blood. This means that the carcinogens will also affect the fetus. They found that the carcinogen levels could be influenced by living close to a highway, second hand smoke exposure, and living close to industrial chimneys.

Video: Tumor-suppresor and oncogenes

http://www.youtube.com/watch?v=eoWRZbtqB_s

Proto-oncogenes and tumor-suppresor genes are what regulate cell division. However, proto-oncogenes can turn into oncogenes if they are mutated. Oncogenes are bad because they stimulate excessive division. When tumor-suppresor genes get mutated, they could become inactive, so it won't slow down the division. Mutations of these genes can cause cancer, which is uncontrolled division of the cells. These genes are discussed in section 14.3.

Animation: Nucleotide Excision Repair

http://highered.mcgraw-hill.com/sites/dl/free/0072835125/126997/animation33.html

Nucleotide excision repair (NER) is the cell's way of fixing damage to DNA. First, a protein trimer is added onto the double helix. It “scans” the molecule for damage. When it finds the damage, one protein stays on and two are released. Then, a protein binds to this site and makes two cuts on the strand, which are several bases away from the damaged part. Then, a helicase binds to that site and separates the damaged part from the rest of the DNA. All the proteins are released from the strand. Now, there is a gap that can be filled in with the proper nucleotides. This process is discussed in section 14.2.