Recombination and Genome Rearrangements
Published Online: 15 SEP 2006
Copyright © 2006 Wiley-VCH Verlag GmbH & Co. KGaA. All rights reserved.
Reviews in Cell Biology and Molecular Medicine
How to Cite
Klein, H. L. 2006. Recombination and Genome Rearrangements. Reviews in Cell Biology and Molecular Medicine. .
- Published Online: 15 SEP 2006
Homologous recombination (HR) is an essential activity of all cells as it is one of two major pathways used to repair potentially lethal double-strand breaks (DSBs). DSBs arise from many sources. They may be induced by exogenous agents such as ionizing radiation or chemicals that modify the DNA bases of the DNA backbone, such as methylmethane sulfonate, bleomycin, or mitomycin C. Agents that inhibit DNA topoisomerases, such as cisplatin, also cause DSBs. Endogenous DSBs may occur from programmed breaks, such as those involved in immune system V(D)J recombination of vertebrates, faulty topoisomerases, or oxygen free radicals. When the DNA replication apparatus encounters bulky lesions or a nicked template strand, DSBs may form, collapsing the replication fork. Alternatively, the replication fork may stall with single-strand DNA at the fork. This is a substrate for HR, or further processing to form a DSB. These DSBs are repaired by HR or nonhomologous DSB rejoining events. Therefore, although mitotic HR occurs at significantly reduced rates compared to meiotic HR, it is nonetheless an essential aspect of vegetative growth.
HR is essential for maintaining integrity of the genome, for preventing chromosome rearrangements, for preventing changes in chromosome number, for telomere maintenance when the normal telomere replication pathway is defective, and for preventing the occurrence of alternate double-strand break repair pathways that may result in loss of heterozygosity (LOH) events. Since spontaneous DSBs occur in every replication cycle in vertebrate cells, HR is an essential function of a normal replication cycle. Meiotic HR may also be linked to repairing premeiotic DNA replication errors, but its main purpose lies in ensuring genetic variation and proper chromosome segregation. Meiotic HR gives genetic variation to future generations by providing new combinations of alleles in the gametes. The most important function of meiotic HR is to provide a mechanism for proper segregation of homologous chromosomes at the first meiotic division. In the absence of crossing-over, chromosomes do not disjoin at the first meiotic division and give rise to aneuploid meiotic products. In this chapter, the current models for double-strand break repair by HR are reviewed, differences between mitotic and meiotic HR are discussed, and the consequences of defective HR are considered.
- Gene Conversion;
- Holliday Junction;
- Mismatch Repair;
- Nonhomologous End Joining;
- Strand Exchange;