Medical Genetics - V. M. Zaporozhan 2005

Basics of Oncogenetics
Targets of Gene Action Involved in Carcinogenesis
Mutator Genes

Mutator genes encode DNA Repair Enzymes. When these genes undergo mutation and DNA repair is impaired, the mutation frequency in Cells increases thousands of times. The Emergence of Mutations leading to tumor formation becomes only a matter of time.

The best-known pathology associated with mutations in these genes is xeroderma pigmentosum. It is a group of Autosomal Recessive Disorders caused by mutations in the genes encoding DNA Excision Repair enzymes. Under METABOLISM/18.html">The Influence of ultraviolet rays, thymine dimers can form in DNA. Excision repair enzymes excise the damaged DNA strand segment and restore it using the second complementary undamaged strand. In this disease, DNA repair is impaired. Xeroderma pigmentosum is characterized by The Development of multiple Skin tumors in areas exposed to sunlight.

DNA excision repair enzymes correct defects caused not only by UV radiation but also by other mutagens/carcinogens. However, the incidence of Other forms of tumors in xeroderma pigmentosum does not increase. This is believed to indicate that environmental Chemical Mutagens play a minor role in the development of this pathology.

Examples of other hereditary syndromes caused by DNA repair defects include Lynch syndrome, Bloom syndrome, ataxia-telangiectasia, and others. Mutant mutator genes are also responsible for the development of hereditary nonpolyposis Colorectal Cancer (see Table 8.3).

Mutations in suppressor genes that control apoptosis also increase genetic instability because they allow cells with unrepaired mutations to survive.