Question

Q2. Cell division cycle mutations render the mutants unable to continue the cell cycle. This phenotype creates a paradox where mutant cells must also be grown in the lab to further identify the gene and study the role of the protein. How do you think this problem can be solved?

Q5. Although mutations have been observed in many different genes, they have not been isolated in histones. Why does this seem reasonable? If one wanted to produce antibodies to histones, would it be an easy task? Explain your answer.

Q6. It is possible to take the DNA of a gene from any source and place it on a chromosome in the nucleus of a yeast cell. When you take DNA of a human gene and put it into a yeast cell chromosome, the yeast cell can synthesize the human protein. However, when you remove the DNA for a gene normally present on yeast mitochondrial chromosomes and put it on a yeast chromosome in the nucleus, the yeast cell cannot synthesize the correct protein, even though the gene comes from the same organism. Explain. What would you need to do to ensure that such a yeast cell could make the correct protein?    

Q9. Describe the general relationship that may exist between mutations and cancer.

      

Answer 1

Ans9:- Cancer is a result of the breakdown of the controls that regulates ccells. The cause of the breakdown always include in importat genes. These chahnges are often the result of mutations, changes in the DNA sequence of chromosomes. Mutation can be vvvery small changes affecting only a few nucleotides or they can be ery large, leading to major changes in the structure of chromosomes.

The abnormal behaviors demonstrated by cancer cells are the result of a series of mutations in key regulatory genes. The cells become progressively more abnormal as more genes become damaged. Often, the genes that are in control of DNA repair become damaged themselves, rendering the cells even more susceptible to ever-increasing levels of genetic mayhem.

Most cancers are thought to arise from a single mutant precursor cell. As that cell divides, the resulting 'daughter' cells may acquire different mutations and different behaviors over a period of time. Those cells that gain an advantage in division or resistance to cell death will tend to take over the population. In this way, the tumor cells are able to gain a wide range of capabilities that are not normally seen in the healthy version of the cell type represented. The changes in behavior seen in cancer cells are the focus of the Cancer Biology section of the site.

Mutations in key regulatory genes (tumor suppressors and proto-oncogenes) alter the behavior of cells and can potentially lead to the unregulated growth seen in cancer.

Inherited Mutations in Cancer

To complicate matters, it is clear that the changes needed to create a cancer cell can be accomplished in many different ways. Although all cancers have to overcome the same spectrum of regulatory functions in order to grow and progress, the genes involved may differ. In addition, the order in which the genes become de-regulated or lost may also vary. As an example, colon cancer tumors from two different individuals may involve very different sets of tumor suppressors and oncogenes, even though the outcome (cancer) is the same.

The great heterogeneity seen in cancer, even those of the same organ, means that diagnosis and treatment are complicated. Current advances in the molecular classification of tumors should allow the rational design of treatment protocols based on the actual genes involved in any given case. New diagnostic tests may involve the screening of hundreds or thousands of genes to create a personalized profile of the tumor in an individual. This information should allow for the tailoring of cancer treatments geared to the individual. For more information on this see the Genomics/Proteomics section.

The genetic changes that lead to unregulated cell growth may be acquired in two different ways. It is possible that the mutation can occur gradually over a number of years, leading to the development of a 'sporadic' case of cancer. Alternatively, it is possible to inherit dysfunctional genes leading to the development of a familial form of a particular cancer type. Some examples of cancers with known hereditary components include:

• Breast cancer- Inheritance of mutant versions of the BRCA1 and BRCA2 genes are known risk factors. Although many, if not most, individuals with breast cancer do not have detectable alterations in these genes, having a mutant form increases the likelihood of developing breast cancer.
• Colon cancer- Defects in DNA repair genes such as MSH2 are known to predispose individuals to hereditary non-polyposis colorectal cancer (HNPCC).
• Retinoblastoma- Defects in the Rb tumor suppressor gene are known to cause this eye cancer and several other types of cancers. More on this particular disease can be found in the section on Rb

This is an incomplete list of the known inherited cancer types, and it is certain that more inherited forms of cancer will identified as the genetics of various types of cancer are clarified.

More information on this topic may be found in Chapters 2 and 4 of The Biology of Cancer by Robert A. Weinberg.

Types of Mutation

The process by which proteins are made, translation, is based on the 'reading' of mRNA that was produced via the process of transcription. Any changes to the DNA that encodes a gene will lead to an alteration of the mRNA produced. In turn, the altered mRNA may lead to the production of a protein that no longer functions properly. Even changing a single nucleotide along the DNA of a gene may lead to a completely non-functional protein.

There are several different ways DNA can be altered. The following section describes the different types of genetic change in more detail.

Point Mutations

Genetic alterations can be placed into two general categories. The first category is comprised of changes that alter only one or a few nucleotides along a DNA strand. These types of changes are termed point mutations.

When ribosomes read a messenger RNA molecule, every three nucleotides is interpreted as one amino acid. These three letter codes are called codons. To make an analogy to an English sentence: 'The fat cat ate the rat' would contain 6 codons. The changes caused by mutation can lead to things like 'The fat bat ate the rat.' or 'The fa' or 'The fat oca tat her at...' The impact on the protein depends on where the change occurs and the kind of change.

The three-letter codons read by ribosomes may be changed by mutation in one of three ways:

Nonsense mutations

The new codon causes the protein to prematurely terminate, producing a protein that is shortened and often does not function properly or at all.

Missense mutations

The new codon causes an incorrect amino acid to be inserted into the protein. The effects on the function of the protein depend on what is inserted in place of the normal amino acid.

Frameshift mutations

The loss or gain of 1 or 2 nucleotides causes the affected codon and all of the codons that follow to be misread. This leads to a very different and often nonfunctional protein product.