The Role of Mitotic Recombination in Carcinogenesis

Abstract

Genetic recombination systems are present in all living cells and viruses and generally contribute to their hosts' flexibility with respect to changing environmental conditions. Recombination systems not only help highly developed organisms to protect themselves from microbial attack via an elaborate immune system, but conversely, recombination systems also enable microorganisms to escape from such an immune system. Recombination enzymes act with a high specificity on DNA sequences that either exhibit extended stretches of homology or contain characteristic signal sequences. However, recombination enzymes may rarely act on incorrect alternative target sequences, which may result in the formation of chromosomal deletions, inversions, translocations, or amplifications of defined DNA regions. This review describes the characteristics of several recombination systems and focuses on the implication of aberrant recombination in carcinogenesis. The consequences of mitotic recombination on the inappropriate activation of protooncogenes and on the loss of tumor suppressor genes is discussed. Cases are reported where mitotic recombination clearly has been associated with carcinogenesis in rodents as well as humans. Several test systems able to detect recombinagenic activities of chemical compounds are described.

Key Words:

• chromosomal rearrangements
• site-specific recombination
• protooncogenes
• tumor suppressor genes
• recombination test systems
• loss of heterozygosity