Genetic recombination shuffles genetic material, creating new DNA sequence combinations. Mitotic recombination is a specific type of this genetic shuffling, occurring in non-reproductive cells during their normal life cycle. This process plays a significant role in maintaining cellular health and stability by facilitating DNA repair and ensuring genome integrity.
Understanding Mitotic Recombination
Mitotic recombination occurs in somatic cells—all body cells except reproductive ones—during mitosis. Mitosis is the cell division process for growth, repair, and cell replacement. The primary function of mitotic recombination is to repair damaged DNA and maintain genome stability.
This process differs from meiotic recombination, which occurs in germ cells during meiosis to produce sperm and egg cells. Meiotic recombination drives genetic diversity in offspring by shuffling genes for sexual reproduction. In contrast, mitotic recombination maintains genetic stability within an individual’s somatic cells, rather than creating new genetic variations for inheritance.
Mechanisms of Mitotic Recombination
Mitotic recombination primarily occurs through homologous recombination (HR), a pathway that precisely repairs DNA double-strand breaks (DSBs). DSBs are severe DNA damage where both DNA strands are broken, occurring spontaneously or due to damaging agents. For accurate repair, HR uses a homologous template, typically the sister chromatid, an identical copy formed during DNA replication. This restores genetic information without loss.
Within HR, mechanisms like synthesis-dependent strand annealing (SDSA) are common in mitotic cells, often resulting in non-crossover products. Another outcome is gene conversion, where genetic information is non-reciprocally transferred between chromosomes during repair. Less frequent is recombination between non-sister homologous chromosomes, which can lead to specific genetic changes like loss of heterozygosity.
Mitotic Recombination and Its Implications
Mitotic recombination has significant consequences for cellular health, with both beneficial aspects and potential contributions to disease. Its main beneficial role is in DNA repair, precisely fixing double-strand breaks, maintaining genomic integrity, and preventing harmful mutations. This repair is active during the S and G2 phases of the cell cycle, when sister chromatids are available as templates.
Despite its protective role, mitotic recombination can contribute to diseases, such as cancer. This occurs through “loss of heterozygosity” (LOH). LOH happens when a cell with two different gene versions loses one, leading to the remaining allele’s expression.
If the lost allele was a functional tumor suppressor gene and the remaining one is mutated, LOH can inactivate the tumor suppressor, accelerating tumor progression. For instance, LOH at the TP53 locus is commonly observed in human cancers and can lead to tumor predisposition. Mitotic recombination is a major contributor to spontaneous LOH events in somatic cells.