Question

How do normal cells protect themselves from accumulating mutations in genes that could lead to cancer? How do cancer cells differ from normal cells in these processes?

Short answer

Answer: Normal cells use several protective mechanisms to prevent accumulation of mutations that could lead to cancer, including DNA repair mechanisms, cell cycle checkpoints, apoptosis, and tumor suppressor genes. Cancer cells often differ from normal cells in these protective mechanisms, showing impaired DNA repair, dysregulation of cell cycle checkpoints, resistance to apoptosis, and inactivation of tumor suppressor genes. These differences facilitate cancer cells' uncontrolled growth and ability to invade other tissues.

Step-by-step solution

1. Introduction to mutations and cancer

Mutations are changes in the DNA sequence that can result from various factors such as exposure to radiation, chemicals, or errors during DNA replication. Some mutations can lead to the development of cancer, which is characterized by uncontrolled cell growth and the ability to invade other tissues. Normal cells have mechanisms in place to prevent the accumulation of these mutations and protect themselves from developing into cancer cells.

2. Protective mechanisms in normal cells

There are several mechanisms that normal cells use to protect themselves from accumulating mutations that could lead to cancer: a. DNA repair mechanisms: Cells have specific repair systems that can detect and repair DNA damage or errors. Examples include base excision repair, nucleotide excision repair, and mismatch repair. b. Cell cycle checkpoints: The cell cycle is controlled by a series of checkpoints that ensure proper progression through the phases and prevent cells with DNA damage from dividing. Checkpoints exist at the G1/S transition, intra-S phase, and G2/M transition. c. Apoptosis: Also known as programmed cell death, apoptosis is a process that leads to the controlled elimination of cells with severe DNA damage or errors, preventing them from forming cancer cells. d. Tumor suppressor genes: These are genes that help control cell division, preventing the formation of cancer cells. When these genes are functional, they can suppress the development of tumors. Examples include the p53 and BRCA1/2 genes.

3. Differences between normal and cancer cells in protective mechanisms

Cancer cells differ from normal cells in the following aspects of these protective mechanisms: a. Impaired DNA repair: Cancer cells often have defects in their DNA repair systems, leading to the accumulation of mutations that can promote cancer development further. b. Dysregulation of cell cycle checkpoints: Many cancer cells have alterations in their cell cycle control mechanisms, allowing them to bypass critical checkpoints that would otherwise prevent them from dividing with damaged DNA. c. Resistance to apoptosis: Cancer cells can develop resistance to apoptotic signals, enabling them to survive and proliferate despite having DNA damage or errors. d. Inactivation of tumor suppressor genes: In many cases, cancer cells have mutations that inactivate tumor suppressor genes, relieving the constraints on cell division and promoting uncontrolled proliferation. In conclusion, normal cells have multiple protective mechanisms in place to prevent the accumulation of mutations that could lead to cancer. Cancer cells, on the other hand, often have defects or alterations in these mechanisms that facilitate their uncontrolled growth and ability to invade other tissues.

Key concepts

DNA repair mechanisms

DNA repair mechanisms play a crucial role in maintaining the integrity of the genetic material within our cells. Every day, our DNA is subjected to potential damaging agents like UV light or chemicals. Fortunately, cells have developed efficient repair systems that identify and fix these errors.
Base excision repair, nucleotide excision repair, and mismatch repair are among these vital systems. These mechanisms work tirelessly to scan the DNA for damage. Once damage is detected, they cut out the faulty segments and replace them with the correct sequences.

• Base excision repair deals with small, non-helix distorting lesions.
• Nucleotide excision repair fixes bulky, helix-distorting lesions like thymine dimers.
• Mismatch repair corrects errors that escape during DNA replication.

These mechanisms are vital for preventing mutations that can lead to cancer. However, in cancerous cells, these systems often become impaired, allowing mutations to accumulate.

Apoptosis

Apoptosis is the process of programmed cell death, a natural way for the body to eliminate unhealthy or damaged cells. In normal cells, when DNA damage is beyond repair, apoptosis is activated to prevent the damaged cell from dividing.
This process involves a series of controlled steps that lead to the orderly dismantling of cellular components. This prevents damage to the neighboring cells and ensures that potentially cancerous cells are removed.
Apoptosis is characterized by cell shrinkage, DNA fragmentation, and membrane blebbing. Cancer cells often bypass this process, enabling them to survive despite possessing genetic errors. The resistance to these apoptotic signals is a hallmark of cancerous growth, contributing to the unchecked proliferation of cells.

Tumor suppressor genes

Tumor suppressor genes are a category of genes that help regulate cell growth and division. They act as brakes for cell proliferation, ensuring that cells divide only when necessary and under controlled circumstances.
Key players include the p53 and BRCA1/2 genes, which act to repair DNA, regulate the cell cycle, and induce apoptosis if damage is irreparable. When functioning correctly, these genes are oncogene inhibitors, keeping cancer development in check.
However, mutations that inactivate tumor suppressor genes remove these critical controls. This incapacity to regulate cell division efficiently can lead to uncontrolled cell growth, a characteristic feature of cancer development. Understanding the function of these genes is essential in developing cancer therapies.

Cell cycle checkpoints

Cell cycle checkpoints are surveillance mechanisms that regulate the progression of cells through the cell cycle. These checkpoints ensure that each phase is completed accurately before moving onto the next one. They prevent cells with damaged DNA from replicating.
There are three main checkpoints:

• The G1/S checkpoint ensures that the cell has all the resources it needs and its DNA is intact before replication.
• The intra-S phase checkpoint monitors any issues that arise during DNA replication.
• The G2/M checkpoint ensures that all DNA is correctly replicated and undamaged before entering mitosis.

Cancer cells often manipulate these checkpoints, allowing them to bypass normal controls. This dysregulation leads to the proliferation of cells with genetic abnormalities, thereby contributing to cancer progression. Safeguarding these checkpoints is crucial for maintaining cellular integrity and preventing cancer.