Question

How can breakdown in DNA repair play a role in the development of human cancers?

Short answer

Defective DNA repair leads to mutations, often in oncogenes or tumor suppressor genes, causing uncontrolled cell division and potentially cancer.

Step-by-step solution

- Understand DNA Repair

DNA repair mechanisms are crucial processes that correct damage to the DNA molecules that encode our genomes. Basic types of DNA repair include base excision repair, nucleotide excision repair, mismatch repair, and double-strand break repair. These mechanisms ensure the integrity and stability of the genetic material.

- Identify How DNA Damage Occurs

DNA damage can be caused by various factors such as UV light, radiation, chemicals, and reactive oxygen species. It can lead to mutations if not properly repaired. Mutations in critical genes can disrupt normal cellular processes.

- Link DNA Repair Defects to Mutations

When DNA repair mechanisms fail or are insufficient, this leads to the accumulation of DNA damage. Mutations can then occur in oncogenes (genes that promote cell growth) or tumor suppressor genes (genes that inhibit cell growth), leading to uncontrolled cell division.

- Explain the Connection to Cancer

Defective DNA repair mechanisms are often linked to the accumulation of genetic mutations, which can result in the activation of oncogenes or the inactivation of tumor suppressor genes. This can initiate the development of cancer, as cells begin to grow and divide uncontrollably.

- Provide Examples

Examples of cancer syndromes that result from defects in DNA repair include Xeroderma Pigmentosum, which is related to problems in nucleotide excision repair, and hereditary nonpolyposis colorectal cancer (Lynch syndrome), which is linked to defects in mismatch repair.

Key concepts

DNA repair mechanisms

DNA repair mechanisms are crucial processes that correct damage to DNA molecules, ensuring the integrity and stability of genetic material. These processes can fix errors that occur during DNA replication or environmental damage. For example, base excision repair, nucleotide excision repair, and mismatch repair are all types of DNA repair mechanisms. Without these processes, our cells would accumulate damage, potentially leading to cancer.

genetic mutations

Genetic mutations are changes in the DNA sequence. These can be caused by errors during DNA replication or by damage from environmental factors like UV light or chemicals. If mutations are not repaired correctly, they can lead to changes in the function of crucial genes. Some mutations can be benign, but others can disrupt cellular processes and contribute to the development of diseases like cancer.

oncogenes

Oncogenes are genes that, when mutated, have the potential to cause normal cells to become cancerous. They usually play a role in cell growth and division. Under normal conditions, these genes help cells grow at a controlled rate. However, if they become mutated, they can promote uncontrolled cell division. This uncontrolled growth is a hallmark of cancer development.

tumor suppressor genes

Tumor suppressor genes act as the brakes of cell division. They help to prevent uncontrolled cell growth by repairing DNA mistakes or initiating cell death if the DNA damage is irreparable. When these genes are mutated or inactivated, the control over cell division is lost, leading to the potential for cancerous growth. Examples include the TP53 gene, which is crucial for controlling cell death and repair mechanisms.

nucleotide excision repair

Nucleotide excision repair (NER) is a DNA repair mechanism that removes bulky lesions that have distorted the DNA helix. These lesions can be caused by UV light or chemical exposures. NER excises a short single-strand segment containing the lesion and fills the gap with newly synthesized DNA using the undamaged strand as a template. Impairments in this repair mechanism can lead to conditions like Xeroderma Pigmentosum, increasing the risk of skin cancers.

mismatch repair

Mismatch repair (MMR) corrects errors that escape the proofreading activity of DNA polymerases during DNA replication. These errors include misincorporated bases and small insertions or deletions. MMR increases the fidelity of DNA replication by recognizing and repairing these mismatches. Defects in MMR can lead to a buildup of replication errors, contributing to hereditary nonpolyposis colorectal cancer (Lynch syndrome).

cancer syndromes

Cancer syndromes are hereditary conditions associated with higher risks of developing specific cancers. They often result from inherited defects in DNA repair mechanisms. For example, Xeroderma Pigmentosum is linked to defects in nucleotide excision repair, leading to extreme sensitivity to UV light and a high risk of skin cancers. Lynch syndrome results from defects in mismatch repair genes, significantly increasing the risk of colorectal and other types of cancer.