Bio 221 Chapter 13: Altering the Genetic Material- Mutation, DNA Repair and Cancer

DNA repair systems: Base excision and nucleotide excision repair

Base excision and nucleotide excision repair - An abnormal base or nucleotide is recognized and a portion of the strand containing the abnormality is removed. The complementary DNA strand is then used as a template for synthesizing a normal DNA strand.

Define benign tumor

Benign tumor: a precancerous mass

What are the effects of mutations that occur outside of the coding sequence of a gene? Intergenic region

Intergenic region - not as likely to affect gene expression

Describe ionizing radiation

Ionizing radiation - Radiation of short wavelength and high energy, ionizing radiation, is known to alter DNA structure. This type of radiation can penetrate deeply into biological materials, where it creates free radicals. Exposure to high doses of ionizing radiation can cause base deletions, breaks in one DNA strand, or even a break in both DNA strands.

What are spontaneous mutations? Give examples of spontaneous mutations.

Spontaneous mutations are the result of abnormalities in biological processes. ● Errors in DNA replication ● Toxic metabolic products ● Changes in nucleotide structure ● Transposons

Describe a somatic mutation.

The somatic cells constitute all cells of the body except for the germ line. Mutations can occur within somatic cells at early or late stages of development.

Define tumor

Tumor: an abnormal overgrowth of cells

In which of the following locations is a mutation least likely to affect gene function? a. Promoter b. Coding region c. Splice junction d. Intergenic region e. Regulatory region

d. Intergenic region

The mutagenic effect of UV light is: a. The alteration of cytosine bases to adenine bases b. The formation of adenine dimers that interfere with genetic expression c. The breaking of the sugar-phosphate backbone of the DNA molecule d. The formation of thymine dimers that disrupt DNA replication e. The deletion of thymine bases along the DNA molecule

d. The formation of thymine dimers that disrupt DNA replication

What are the effects of mutations that occur outside of the coding sequence of a gene? List the sequences.

● Promoter ● Transcriptional regulatory element/operator site ● Splice sites ● Translational regulatory element ● Intergenic region

Describe the role of checkpoint proteins, in particular, describe the p53 protein.

-Checkpoint proteins check the integrity of the genome and prevent a cell from progressing past a certain point in the cell cycle. -P53 is a checkpoint protein that controls the ability of cells to advance from the G1 phase of the cell cycle to the S phase. -The expression of pp53 is induced when DNA is damaged. -The p53 protein functions as a regulatory transcription factor that activates several genes, leading to the synthesis of proteins that stop the cell cycle and other proteins that repair the DNA. -If DNA damage is too severe, the p53 protein will also activate the other genes that promote programmed cell death (apoptosis).

List the 3 types of DNA repair systems

1. Direct repair 2. Base excision and nucleotide excision repair 3. Mismatch repair

Describe the general features of a signal transduction pathway involving a growth factor that promotes cell division.

1. Growth factor binds to a receptor, leading to receptor activation. 2. Receptor activation causes a cascade of interactions between intracellular signaling proteins, thereby activating them. 3. The final protein in the signal transduction pathway activated transcription factors in the nucleus. This leads to the transcription of genes that promote cell division.

List the 3 ways an proto-oncogene can be mutated to an oncogene.

1. Missense mutation 2. Gene amplification 3. Chromosomal translocation

What are the two categories of mutant genes relating to cancer?

1. Oncogene - In some cases, a mutation causes a gene to be overactive. This overreactivity contributes to the uncontrolled cell growth that is observed in cancer cells. 2. Tumor-suppressor gene - A normal gene that encodes a protein that helps regulate normal cell growth, thereby preventing cancer. However, when a mutation eliminates its function, uncontrolled cell growth may occur, which is a hallmark of cancer cells.

What are the two gene mutations that alter the DNA sequence of a gene and what do they do?

1. Point mutation - affects only a single base pair within the DNA 2. Base substitution - in which a T has been replaced by a G and the corresponding A in the complementary strand is replaced with a C.

Describe the function of the Ras protein.

1. Ras releases GDP and then binds GTP to become active. 2. The active Ras protein participates in a signal transduction pathway that promotes cell division. 3. GTP hydrolysis returns Ras to an inactive state

Describe the process of the NER system in depth. You can also draw a picture.

1. Two UvrA proteins and one UvrB protein form a complex that tracks along the DNA. Damaged DNA has a distorted double helix, which is sensed by the UvrA-UvrB complex. 2. When the complex identifies a damaged site, the two UvrA proteins are released, and UvrC binds to UvrB at the site. 3. The UvrC protein makes cuts in one DNA strand on both sides of the damaged site. 4. After this incision process, UvrC is released. UvrD functions as a helicase, which is a protein that separates DNA strands from each other. It binds to UvrB. UvrD then begins to separate the DNA strands, and UvrB is released. The action of UvrD unravels the DNA, which removes a short DNA strand that contains the damaged region. UvrD is released. 5. After the damaged DNA strand is removed, a gap is left in the double helix. DNA polymerase fills in the gap using the undamaged strand as a template. Finally, DNA ligase makes the final covalent connection between the newly made DNA and the original DNA strand.

Describe a germ-line mutation.

A germ-line mutation refers to cells that give rise to gametes, such as eggs or sperm cells. If a mutant human gamete participates in fertilization, all cells of the resulting offspring will contain the mutation.

Describe base analogues

Base analogues - 5-Bromouracil and 2-aminopurine are called base analogues, because their structures are similar to those of particular bases in DNA and can substitute them. When incorporated into DNA, they can also cause errors in DNA replication.

Define carcinogens

Carcinogens: agents that increase the likelihood of developing cancer

Describe the following mutation: Changes in nucleotide structure

Changes in nucleotide structure - on rare occasions, the linkage between purines and deoxyribose can spontaneously break; changes in base structure may cause mispairing during DNA replication

Ways an proto-oncogene can be mutated to an oncogene: Chromosomal translocation

Chromosomal translocation - A piece of chromosome may be translocated to another chromosome and affect the expression of genes at the breakpoint site

Describe covalent modification

Covalent modification - Some chemical agents act by covalently modifying the structure of nucleotides.

DNA repair systems: Direct repair

Direct repair - A repair enzyme recognizes an incorrect structure in the DNA and directly restores the correct structure.

Describe distortion of the DNA double helix

Distortion of the DNA double helix - Some chemical mutagens exert their effects by interfering with DNA structure. When distorted DNA is replicated, single nucleotide additions and deletions may be incorporated into the newly made strands.

Describe the following mutation: Errors in DNA replication

Errors in DNA replication - An unrepaired mistake by DNA polymerase may cause a point mutation

Gene mutations that affect the amino acid sequence of a polypeptide: Frameshift mutation

Frameshift mutation- deletion of a number of nucleotides that is not in a multiple of three

Ways an proto-oncogene can be mutated to an oncogene: Gene amplification

Gene amplification - The copy number of a proto-oncogene may be increased by gene duplication.

What are induced mutations? Give examples and descriptions.

Induced mutations are caused by environmental agents that enter the cell and alter the structure of DNA. ● Chemical agents - chemical substances may cause changes in the structure of DNA ● Physical agents - physical agents such as UV light and X-rays can damage DNA

Define malignant tumor

Malignant tumor: additional genetic changes that cause some cells in the tumor to lose their normal growth regulation

Define metastasis

Metastasis: the process of cancer cells spreading throughout the body through the bloodstream or body fluids

DNA repair systems: Mismatch repair

Mismatch repair - Similar to excision repair, except that the DNA defect is a base pair mismatch in the DNA, not an abnormal nucleotide. The mismatch is recognized, and a strand of DNA in this region is removed. The complementary strand is used to synthesize a normal strand of DNA.

Ways an proto-oncogene can be mutated to an oncogene: Missense mutation

Missense mutation - A change in the amino acid sequence of a proto-oncogene protein may cause it to function in an abnormal way.

Gene mutations that affect the amino acid sequence of a polypeptide: Missense mutation

Missense mutation - a base substitution that changes a single amino acid in a polypeptide

Describe non-ionizing radiation

Non-Ionizing radiation - UV light is a type of nonionizing radiation. It contains less energy than ionizing radiation and so it penetrates only the surface of biological materials. UV light can cause the formation of a thymine dimer, which is the site where two adjacent thymine bases become covalently bonded to each other.

Gene mutations that affect the amino acid sequence of a polypeptide: Nonsense mutation

Nonsense mutation - a change from a normal codon to a stop codon

What are the effects of mutations that occur outside of the coding sequence of a gene? Promoter

Promoter - may increase or decrease the rate of transcription

Define proto-oncogene

Proto-oncogene: a normal gene that, if mutated, can become an oncogene

Gene mutations that affect the amino acid sequence of a polypeptide: Silent mutation

Silent mutation- does not alter the amino acid sequence of the polypeptide, even though the nucleotide sequence has been changed

What are the effects of mutations that occur outside of the coding sequence of a gene? Splice sites

Splice sites - may alter the ability of pre-mRNA to be properly spliced

Describe the following mutation: Toxic metabolic products

Toxic metabolic products - the products of normal metabolic processes may be reactive chemicals that alter the structure of DNA

What are the effects of mutations that occur outside of the coding sequence of a gene? Transcriptional regulatory element/operator site

Transcriptional regulatory element/operator site - may alter the regulation of transcription

What are the effects of mutations that occur outside of the coding sequence of a gene? Translational regulatory element

Translational regulatory element - may alter the ability of mRNA to be translationally regulated

Describe the following mutation: Transposons

Transposons - DNA transposons are small segments of DNA that can insert at various sites in the genome; if they insert into the gene, they may inactivate it

Define oncogene

a gene that has the potential to cause cancer

Researchers have identified a drug that prevents the Ras protein from hydrolyzing GTP. How would this drug affect the growth factor signaling pathway? How would it affect growth? a. The signaling pathway would stay turned on and cell growth would be stimulated b. The signaling pathway would stay turned on and cell growth would be inhibited c. The signaling pathway would be turned off and cell growth would be stimulated d. The signaling pathway would be turned off and cell growth would be inhibited e. None of the above would occur

a. The signaling pathway would stay turned on and cell growth would be stimulated

A mutation changes a proline codon (CCG) into a threonine codon (ACG). This is an example of: a. A silent mutation b. A missense mutation c. A nonsense mutation d. A frameshift mutation e. Both B and C

b. A missense mutation

If a mutation eliminated the function of UvrC, which function of nucleotide excision repair would not work? a. Sensing a damaged DNA site b. Cutting off the damaged strand c. Removal of the damaged strand d. Synthesis of the new strand, using the undamaged strand as a template e. None of the above

b. Cutting off the damaged strand

Cancer cells are said to be metastatic when they: a. Begin to divide uncontrollably b. Invade healthy tissue c. Migrate to other parts of the body d. Cause mutations in other healthy cells e. Do all of the above

c. Migrate to other parts of the body

Mutagens can cause mutations by: a. Chemically altering DNA nucleotides b. Disrupting DNA replication c. Altering the genetic code of an organism d. All of the above e. A and B only

e. A and B only

How do mutagens affect DNA structure? List all possibilities

● Covalent modification ● Base analogues ● Distortion of the DNA double helix ● Ionizing radiation ● Non-Ionizing radiation