Genetics Cancer HW

Select the events that are a consequence of activating mutations in the ras gene.

-Specific transcription factors are activated by phosphorylation. -Abnormally rapid cell growth and proliferation is induced. -The ras proto-oncogene is converted into an oncogene. The Ras signaling pathway is activated by growth factors that bind to specific receptors on the cell surface. In the absence of growth factors, Ras is inactive and is bound to guanosine diphosphate (GDP). When growth factors bind to the membrane receptors, the GDP bound to Ras is exchanged for guanosine triphosphate (GTP) with the help of nucleotide exchange factors. Ras bound to GTP is in an active form that in turn activates a cascade of mitogen-activated protein (MAP) kinases. The MAP kinases phosphorylate and activate specific transcription factors. Activated transcription factors up regulate the expression of genes that are essential for cell growth and proliferation. Ras signaling is terminated when the GTP bound to Ras is hydrolyzed to GDP. Deregulation of the Ras signaling pathway by mutations in the ras gene are observed in a majority of cancers. A normally functioning Ras gene is considered a proto-oncogene because its activity promotes cell division. Activating mutations in the Ras proto-oncogene convert it into an oncogene. Oncogenes are drivers of cancer formation and progression. Mutations in Ras prevent the hydrolysis of GTP, so the Ras pathway remains continuously, or constitutively, active. The constitutive activation of Ras results in the constitutive transcription of target genes that results in uncontrolled growth and eventual malignant transformation of normal cells.

How might a mutation in a gene that regulates telomerase lead to cancer?

-The mutation could allow telomerase to be expressed when it should not be. telomerase is not expressed in most of the normal human cells, after several mutations the activation of telomerase occurs and expressed when it is not required.

1. DNA damage checkpoints are crucial for preventing cell proliferation when DNA damage has occurred. The role of DNA checkpoint proteins in the cell cycle is closely tied to the roles of DNA repair enzymes, although these proteins perform different functions. 2. Which cell cycle phases contain critical DNA damage checkpoints?

-These proteins prevent the cell cycle from progressing if damaged DNA is detected. -G1, G2, and M

Select the mechanisms used by tumor suppressor proteins to prevent the initiation and progression of cancer.

-They act at cell cycle checkpoints to regulate progression through the cycle. -They induce apoptosis in response to DNA damage. -They repair base substitutions or breaks in DNA

Which of the mutations described have the potential to cause cancer?

-a gain‑of‑function mutation in a proto‑oncogene -a loss‑of‑function mutation in a tumor suppressor gene Both tumor suppressors and proto‑oncogenes are genes that could cause cancer when mutations disrupt the function of the normal gene product. Proto‑oncogenes promote cell growth and division. Gain‑of‑function mutations in proto‑oncogenes either increase the rate of expression or activity or result in expression at inappropriate times. When such a mutation is present, the gene is called an oncogene. Because one mutant copy of the gene can cause increased gene activity, oncogenes may cause cancer in a dominant manner. In contrast, a loss‑of‑function mutation in a proto‑oncogene would inhibit or slow down cell division and help to prevent cancer. Tumor suppressor genes slow the rate of cell division or inhibit cell division at particular times. Some tumor suppressor genes, such as TP53, also halt cancerous growth by inducing apoptosis of cells with DNA damage that might cause cancer. Typically, loss‑of‑function mutations in tumor suppressor genes are associated with cancer. Because one copy of a normally functioning tumor suppressor gene is functional in a heterozygote, loss‑of‑function mutations in tumor suppressor genes are recessive. Proto‑oncogenes are often compared to the accelerator on a vehicle, and tumor suppressor genes are often compared to brakes. One type of gene can moderate the effects of the other type. The presence of a single copy of an oncogene or the deletion of both copies of a tumor suppressor gene in a cell does not necessarily cause cancer. Cancerous cells often have both oncogenes and mutations in tumor suppressor genes. -Tumor supressor gene:- These are normal genes which slow down the cell division, repair errors in DNA, or instructs cells when to go for apoptosis (or programmed cell death) . When the tumor suppressor genes don't work properly, cells go out of control, and this may lead to cancer. Most cancers occurs due to inactivating mutations in one or more proteins which usually helps to restrict the progress by G1 stage of the cell cycle. p53 is also a such protein which usually helps at major cell-cycle checkpoints, by stopping the cycle if a previous step has gone wrong or if DNA is damaged. So if there is alteration or mutation in this gene there will be loss of fucntion mutation or inactivation of p53 leading to cancer. Protooncogenes:- Proto-oncogenes in a cell usaully has many functions like coding for proteins which stimulate cell division, prevents cell differentiation or regulate programmed cell death (apoptosis). These things are essential for normal growth, development and the maintenance of healthy organs and tissues. But when mutation occurs in these genes they increase the production of these proteins, as a result there will be unregulated cell division, a slower rate of cell differentiation and cell death will be inhibited, so all these will lead cell towards cancer So activation, of a proto-oncogene into an oncogene is gain-of-function mutation. Example of this is " ras "gene,it is a proto-oncogene , it encodes the intracellular signal-transduction proteins, mutation in ras starts producing excessive or uncontrolled growth-promoting signals.leading to cancer , here it is a gain of function mutation. A major difference between oncogenes and tumor suppressor genes is that oncogenes or the cancer causing genes -develop from the activation (turning on) of proto-oncogenes, but tumor suppressor genes cause cancer when they are inactivated (turned off).

Place the events that control the progression of cells through the G1/S checkpoint of the cell cycle in order.

1) cycline D and E binds to CDK proteins 2) cycline-CDK complexes phosphorylates RB protein. 3) inactivated Rb releases active E2F protein. 4) E2F transcribes genes required for DNA replication.

Which statement is true of cyclins? True for Cyclin-dependent Kinase?

1. The levels of cyclin oscillate during the course of the cell cycle. 2. They regulate the cell cycle by phosphorylating other proteins.

Match the checkpoint to its function. G1/S checkpoint

G1/ S check point- maintain cells until necessary enzymes for replication are synthesised. G2/M check point -detection of DNA damage after replication ,(and prevents cells from entering mitosis when DNA is damaged.) Spindle assembly check point- ensure that each chromosome is attatched to spindle fibers from opposite poles. check points are - transition points during cell cycle that ensures all cellular components are functioning properly. ( check proteins identify the issues and leads to arrest the cell cycle and allow adequate time to fix the problems on DNA)

Many cancer cells are immortal because they have mutations that allow telomerase to be constitutively expressed, allowing cancer cells to divide indefinitely. How might this knowledge be used to design an anticancer drug?

Many cancer cells are immortal because they have mutations that allow telomerase to be constitutively expressed, allowing cancer cells to divide indefinitely. How might this knowledge be used to design an anticancer drug?

Match each definition with the corresponding term concerning genes involved in tumor formation.

Match each definition with the corresponding term concerning genes involved in tumor formation. Proto‑oncogenes: -a normal gene that drives inappropriate cell division if abnormally overexpressed Oncogenes: -a mutated gene that promotes inappropriate cell division and tumor formation Tumor suppressor genes: -a gene that normally functions to prevent inappropriate cell division Haploinsufficiency: -a condition in which a single copy of a gene fails to produce enough gene product for normal function

How does cancer differ from most other genetic disorders?

Most genetic disorders are inherited through germ cells from parents. Most cancers are, to some extent, the result of mutations in somatic cells that occur during an organism's lifetime.

Li-Fraumeni Syndrome, or LFS, is an inherited cancer disorder that is caused by heterozygous mutations in the p53 gene. LFS patients are highly prone to bone, muscle, blood, adrenal glands, and brain cancers. Select the mechanism that explains the development of different types of cancers in LFS patients with mutations in the p53 gene.

Mutations in p53 affect checkpoint response in all cells of the body.

Assume that the provirus in the figure inserts just upstream of a tumor‑suppressor gene. Would this likely cause cancer? Why or why not?

NO, the provirus likely has a strong promoter that will cause the over-expression of tumor suppressor gene and that overexpressed tumor suppressor gene will restrict the cell growth. -This insertion is unlikely to cause cancer. The provirus contains a strong viral promoter that increases the expression of the gene downstream of the insertion. Increasing the expression of a tumor‑suppressor gene is not likely to cause cancer, because the gene product protects from cancer rather than promotes cancer. This provirus insertion does not produce epigenetic changes.

Suppose Alia recently learned that she inherited a mutant RB1 allele from her mother, who had retinoblastoma. RB1 is a tumor suppressor gene that is related to retinoblastoma. Why would Alia be at higher risk for getting retinoblastoma at an earlier age than her sister, Tiffany, who inherited a normal RB1 allele from their mother?

Nicole would be at higher risk for getting retinoblastoma at an earlier age than her sister because someone with one mutant allele in a tumor suppressor gene only requires a mutation in the one remaining normal allele for tumor to form. As , this single copy of suppressor gene leaves no backup copy in reserve and if the mutation occurs , the tumor will form. A mutant allele does not increases the chances of mutation in normal allele. -A person who inherited two functioning alleles of a tumor suppressor gene needs both alleles to mutate for tumors to develop. Easier to get it since one is already mutated

Which enzyme is responsible for the replication of chromosome ends in germ cells and certain proliferating somatic cells?

Telomerase

A genetic counselor determines that patients with a deletion in a particular region of a chromosome are more likely to develop cancer than other people. Is the gene responsible for the increased risk of cancer a tumor suppressor or a proto-oncogene?

The gene is a tumor suppressor, because tumor suppressor genes includes apoptosis in abnormal cells. -because tumor suppressor genes inhibit or slow the rate of cell division. (a deletion in a chromosome is bad and should not get to that point...there should have been a process to slow cell division so that those errors could be repaired.

In order to pass the G2/M checkpoint the cell must

have its DNA completely replicated and undamaged.