Mechanisms of Cell Repair

Question 1

Xerodema Pigmentosum

Answer 1

Defective nucleotide excision repair (excision endonuclease)

• Rare autosomal-recessive inherited disorder
• characterized by extreme skin sensitivity to UV light, abnormal skin pigmenation
• Skin cancers
• Some patients develop neurological symptoms
• Thymine dimers

Question 2

Cockayne syndrome

Answer 2

Patients with Cockayne syndrome have sun sensitivity, short stature and progressive neurological degeneration, along with early senility. However, the condition is not associated with cancer. Cockayne syndrome is recessively inherited and is due to a defect in transcription-coupled NER. This is a variant of NER and operates during transcription in terminally differentiated cells such as neurons.

Question 3

Defects in Recombination Repair

Answer 3

• Ataxia Telangiectasia
• Bloom’s Syndrome

Both of these disorders are inherited in an autosomal recessive manner, and are characterized by an increased incidence of cancer

Question 4

Ataxia Telangiectasia

Answer 4

Strand breaks - Lymphoma

Patients are immunodeficient and prone to lymphomas due to chromosome breaks. The ATM kinase initiates damage recognition and signaling processes to coordinate repair with cell cycle checkpoints. It is activated after DNA double-strand breaks. Checkpoint dysregulation of the cell cycle can cause severe DNA damage, resulting in chromosome instability and aneuploidy.

Question 5

Bloom syndrome

Answer 5

Defective DNA helicase

Chromosome breaks

patients have a defective DNA helicase and are unable to repair broken replication forks. Patients will show poor growth with are prone to chromosome breaks and cancer susceptibility

Question 6

Fanconi anemia

Answer 6

Strand breaks

Damage-response pathway may act by stabilizing replication forks that encounter blocking lesions or single-strand breaks. Patients have anemia, skeletal deformities and chromosome breakage

Question 7

Lynch Syndrome

Answer 7

Also known as hereditary nonpolyposis colon cancer

Defect in MMR protein results in susceptibility to cancer of the colon and ovaries

Tumors will display microsatellite instability: High instability of short repeated sequences