3.4 Disruption to the cell cycle

3.4

Disruption to the cell cycle

KEY IDEAS

mutagen

The cell cycle generally functions very efficiently, but sometimes it malfunctions, which can cause many issues for an organism. For example, every time a cell replicates its DNA, approximately three errors occur. Most of these errors are detected and repaired, but some remain and become permanent (mutations). DNA can also become damaged through normal metabolic activities or by environmental factors such as radiation or chemicals. Cells themselves can become damaged through complications with apoptosis.

Mutagens

Mutagens are agents that cause a permanent change in the DNA sequence. Mutagens something that include radiation, chemicals and biological agents. Many mutagens can cause deviant cells causes a mutation, either chemical, that eventually lead to cancer or characteristics of cancer cells. physical or biological Radiation Radiation is a form of energy that consists of electromagnetic waves or high-energy particles. Some forms of radiation (such as radio waves) are very low energy and harmless, whereas others (such as UV light or X-rays (Figure 1)) can cause changes in the DNA sequence.

In this topic, you will learn that: ✚ the action of mutagens or genetic predispositions can disrupt the cell cycle ✚ disruptions of the cell cycle can result in uncontrollable cell division such as cancer ✚ malfunctions in apoptosis can produce deviant cell behaviour. FIGURE 1 X-rays can cause DNA mutations. FIGURE 2 Cigarette smoke contains chemicals that cause DNA mutations.

Chemicals Chemical agents include some of the chemicals in cigarette smoke (Figure 2), mustard gas (which has been used in DRAFT ONLY - NOT FOR SALE chemical warfare) and nitrogen oxides. These chemicals react with the genetic material in cells, resulting in a permanent change in the DNA sequence.

Biological agents

Mutagens Radiation X-rays

Ultraviolet (UV) radiation Chemical

Cigarette smoke

Some chemicals in cleaning products (e.g. benzoyl peroxide)

Some chemicals in preserved food (e.g. nitrate preservatives) Chemical warfare agents (e.g. mustard gas)

Viruses are small non-living particles that consist of genetic material surrounded by a protein coat (Figure 3). Viruses are considered to be non-living because they cannot reproduce independently. Instead, they need to insert their genetic material into a host cell and use the host’s organelles to reproduce. Occasionally, the genetic material of the virus can be inserted in an important section of DNA. This can result in the disruption of the normal functioning of the cell.

Biological Viruses Bacteria FIGURE 4 There are different types of mutagens that can disrupt the cell cycle.

Disrupting the cycle

Mutagens can cause changes in DNA, which can make the chromosomes unstable. The chromosomes may break or rearrange, which, in turn, affects the way a cell responds to its chemical signals.

Other agents may change the sequence of the DNA, which affects the unique code that is responsible for protein synthesis. Some of these changes are lethal or cause serious disease, but not all changes in the DNA sequence cause a cell to become cancerous. Many of these permanent changes (mutations) have little or no effect on the cell’s function. The location of a mutation, the size of the mutation and the compounding effect of previous mutations ultimately determine the biological consequences.

FIGURE 3 Viruses are biological agents that can cause DNA mutations. DRAFT ONLY - NOT FOR SALE

mutation

a permanent change to the DNA sequence

A silent mutation is a mutation that causes no change to the amino acids produced by a sequence of DNA in the cell. Other mutations can have a large effect on a cell. A mutation in a section of DNA that is responsible for controlling the checkpoints of the cell cycle can have a significant impact on the cell’s function. An example of this is the section of DNA that codes for the p53 protein, which acts as a tumour suppressor. A healthy cell does not need p53, and so the levels remain low. When a cell is damaged, more p53 is produced, preventing the cell from undergoing mitosis until the DNA is repaired. If the cell cannot be repaired, the p53 can force the cell to undergo an organised cell death (apoptosis). If there is a mutation in the section of DNA that produces the p53 protein, then the protein will not be produced, and the cell will be able to continue to produce more defective cells.

Malfunctions in apoptosis

Within each cell of a multicellular organism is a series of genes that regulate apoptosis. There is a careful balance between the genes that activate apoptosis and those that suppress apoptosis. In many cases, a permanent change or mutation to the cell’s DNA can upset this balance. Often the organism’s immune system identifies the damaged cell and signals the death receptor pathway, resulting in apoptosis of the cell. Occasionally, the genes that initiate apoptosis have also mutated, preventing the cell from undergoing programmed cell death. This allows the cell to grow and reproduce indefinitely. Further mutations can result in the cell growing uncontrollably, causing cancer. Cancer A single change in the DNA sequence does not cause a cell to become cancerous. Most changes are repaired by special proteins such as the BRCA1 or BRCA2 protein. If there is a lot of damage, then some changes may be missed, causing the permanent change that is a mutation.

Characteristics of cancer cells

Because cell replication is highly regulated, a cell cannot become cancerous unless at least five mutations of specific parts of the DNA have occurred. Six of these changes are outlined below. 1 A cancer cell is self-sufficient. Most cells need external signals from other cells before they can undergo mitosis. Cancerous cells can signal themselves to divide. 2 A cancer cell blocks signals that control the checkpoints of mitosis. Proteins such as p53 can prevent mitosis. A mutation in the section of DNA responsible for producing p53 will allow a cell to divide at any time. 3 A cancer cell avoids apoptosis. This is possible because of a mutation in the DNA that controls the cell’s apoptotic pathway. 4 A cancer cell is able to undergo limitless cell cycles. Cancerous cells can divide an unlimited number of times, whereas there is a limit to the number of times healthy cells can divide.

FIGURE 5 This cell is undergoing apoptosis. DRAFT ONLY - NOT FOR SALE

Describe and explain

1 Define ‘mutagen’. 2 Name and provide examples of the three main types of mutagens. 3 Define ‘mutation’. 4 Define ‘apoptosis’. 5 Explain how mutations contribute to an increased risk of a person developing cancer.

BRCA mutations

Two sections of DNA called BRCA (BReast CAncer gene) code for the BRCA1 and BRCA2 proteins.

These proteins are responsible for repairing errors in

DNA. The errors may be a result of the environment (chemical, viral or radiation mutagens) or part of the regular replication process. If these errors cannot be repaired, then they become permanent mutations.

Over time, the mutations can accumulate, causing

CHECK YOUR LEARNING 3.4 Apply, analyse and compare

6 Compare the functions of the p53 protein with that of the BRCA protein.

Design and discuss

7 Discuss the link between smoking and lung cancer. 8 Discuss how understanding the apoptosis pathway can help develop treatments for cancer.

5 A cancer cell has access to nutrients through a good blood supply. Most cancerous cells can encourage blood vessels to grow around them. 6 A cancer cell is able to migrate (metastasise) around the body.

Cancer cells kill the surrounding cells, either by the six changes that can result in a cell becoming cancerous. Because breast tissue in females regularly undergoes mitosis, people who inherit these mutations can have a higher risk of developing breast cancer. 1 Will all people who inherit the BRCA1 or BRCA2 mutations develop breast cancer? Use your knowledge from this chapter to explain your reasoning. CHALLENGE 3.4 smothering them or by using all the surrounding nutrients. This blocks the normal functioning of the body, resulting in the diseased state. Genetic risks of cancer People in some families have a higher than average risk of getting cancer. There are several reasons for this. The members of these families may have inherited mutations in the DNA that is responsible for one of the six changes above. More than 50% of cancers involve missing or damaged sections of DNA that produces the p53 protein. Inheritance of this mutation is rare, but people with this mutation have a higher risk of developing cancer. Other people can inherit mutations in the DNA responsible for repairing DNA. FIGURE 6 The final stages of cancerous cells dividing DRAFT ONLY - NOT FOR SALE