Question

What is the underlying genetic defect that causes seroderma pig. mentosum? How can the symptoms of this disease be explained by the genetic defect?

Short answer

Seroderma pigmentosum arises from a genetic defect in the DNA repair pathway known as nucleotide excision repair. Symptoms of this disease, which include sunburn, skin lesions, and skin cancer, manifest as the body is unable to repair the skin's DNA damage caused by exposure to UV light.

Step-by-step solution

Identify the genetic defect

Seroderma pigmentosum is caused by a genetic defect that impacts the body's ability to repair damage to its DNA. More specifically, there is a problem with the nucleotide excision repair pathway.

Explain how the defect causes the disease symptoms

The nucleotide excision repair pathway is responsible for identifying and repairing a specific type of damage to DNA known as pyrimidine dimers, which can occur as a result of exposure to UV light. When this pathway is defective, the body cannot effectively repair the damage that occurs to the skin when it is exposed to sunlight. This leads to a high risk of sunburn, skin lesions, and skin cancer, which are all symptoms of Seroderma pigmentosum.

Key concepts

Nucleotide Excision Repair

Nucleotide excision repair is a crucial process within cells that helps maintain the integrity of DNA. It scans for and corrects damage, specifically focusing on lesions that cause distortions in the DNA helix structure. Often these lesions are the result of environmental factors, such as ultraviolet (UV) light.

This repair mechanism involves removing a short, single-stranded DNA segment containing the lesion, such as a pyrimidine dimer. After removal, the correct DNA sequence is restored by DNA polymerase enzymes that fill in the gap with the proper nucleotides. Finally, DNA ligase seals the new section. Without efficient nucleotide excision repair, cellular DNA would accumulate harmful mutations.

DNA Repair Mechanisms

DNA repair mechanisms are integral parts of cellular processes, responsible for identifying and correcting damage or errors in the DNA. These mechanisms evolved to maintain genetic stability and prevent mutations, which could lead to diseases.

Key DNA repair strategies include:

• Base Excision Repair: Fixes small, non-helix-distorting base lesions.
• Nucleotide Excision Repair: Primarily corrects bulky, helix-distorting DNA lesions.
• Mismatch Repair: Corrects replication errors, like mispaired bases or small insertion-deletion loops.

Each repair mechanism functions specifically to address particular types of DNA damage, ensuring optimal reliability in genetic information transmission.

Genetic Disorders

Genetic disorders arise from anomalies in the genome and can affect an individual's health, development, or functional ability. Manifesting due to various types of genetic mutations, these disorders can be inherited or occur sporadically.

Common classifications of genetic disorders include:

• Monogenic Disorders: Caused by mutations in a single gene, like cystic fibrosis.
• Chromosomal Disorders: Involves changes in chromosome number or structure, such as Down syndrome.
• Complex Disorders: Stem from a combination of multiple genetic and environmental factors, such as heart disease.

Xeroderma pigmentosum is a monogenic disorder, specifically related to defects in the nucleotide excision repair pathway, highlighting the link between genetic defects and disease.

Pyrimidine Dimers

Pyrimidine dimers form when DNA is exposed to ultraviolet light, causing adjacent pyrimidine bases, such as thymine or cytosine, to bond covalently. This new bond distorts the DNA double helix and disrupts normal base pairing, impairing replication and transcription processes.

Nucleotide excision repair systems are specialized to recognize and remove these distortive dimers. When the repair system is compromised, as seen in xeroderma pigmentosum, the accumulation of these unrepaired dimers can lead to severe skin damage and heightened skin cancer risk due to unmitigated DNA deterioration. The proper functioning of damage diagnostic and repair mechanisms is crucial for preventing such genetic disorders.