Mitotic recombination
Mitotic recombination is a process of genetic recombination that occurs in the mitotic phase of the cell cycle. This biological mechanism is crucial for the repair of damaged DNA and the generation of genetic diversity within somatic cells. Unlike meiotic recombination, which occurs during the formation of gametes and contributes to genetic diversity in offspring, mitotic recombination affects somatic cells and can lead to somatic mosaicism.
Mechanism
Mitotic recombination can occur through several pathways, including the double-strand break repair (DSBR) pathway and the synthesis-dependent strand annealing (SDSA) pathway. In the DSBR pathway, a double-strand break in DNA initiates the recombination process. The broken DNA ends are processed to form single-stranded DNA, which then invades a homologous DNA sequence. This invasion leads to the formation of a Holliday junction, a cross-stranded structure that can be resolved to produce crossover or non-crossover products. In the SDSA pathway, the process is similar, but the invading strand is displaced before the formation of a Holliday junction, leading primarily to non-crossover products.
Functions
The primary function of mitotic recombination is the repair of damaged DNA, ensuring genomic stability. By allowing for the exchange of genetic material between homologous chromosomes, it can correct genetic defects or damage caused by external factors such as radiation or chemicals. Additionally, mitotic recombination contributes to genetic diversity within tissues, which can have implications for evolution and adaptation at the cellular level.
Consequences
While mitotic recombination plays a vital role in DNA repair and genetic diversity, it can also lead to genetic abnormalities. For example, if recombination occurs between non-allelic homologous sequences, it can result in gene duplications, deletions, or translocations, potentially leading to diseases such as cancer. In particular, loss of heterozygosity (LOH) through mitotic recombination can activate oncogenes or inactivate tumor suppressor genes, contributing to tumorigenesis.
Research and Applications
Research into mitotic recombination has provided insights into the mechanisms of DNA repair, the development of genetic diversity, and the origins of certain diseases. Understanding how mitotic recombination is regulated can lead to new therapeutic strategies for diseases caused by genetic abnormalities. For instance, targeting pathways involved in mitotic recombination could enhance the efficacy of treatments for cancer by preventing the repair of DNA in cancer cells, leading to their death.
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Contributors: Prab R. Tumpati, MD