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Homologous recombination

life science Maturity 5-7 Next article →

Homologous recombination is a fundamental biological process used to exchange genetic information between similar molecules of nucleic acids. This process typically involves double-stranded DNA, but it can also involve RNA in some viruses. In many organisms, cells use this mechanism to perform homologous recombinational repair (HRR). This is a way to accurately fix harmful double-strand breaks (DSB), which are breaks that occur on both strands of the DNA molecule. Beyond simple repair, this process is vital for creating genetic diversity. It occurs during meiosis, the specialized cell division used to create gametes like sperm and egg cells.

HR in meiosis
HR in meiosis

The mechanism of homologous recombination follows a specific sequence of molecular events. It begins after a double-strand break occurs in the DNA. First, the cell performs resection, which is the process of cutting away sections of DNA around the 5' ends of the break. This creates overhanging 3' ends. Next, the process moves to strand invasion. During this step, an overhanging 3' end of the broken DNA molecule invades a similar or identical DNA molecule that remains intact. This intact molecule serves as a template for repair. Following strand invasion, the cell follows one of two main pathways: the double-strand break repair (DSBR) pathway or the synthesis-dependent strand annealing (SDSA) pathway.

HR schematic diagram
HR schematic diagram

These pathways result in different outcomes for the genetic material. When homologous recombination is used for DNA repair, it often results in non-crossover products. This means the process effectively restores the damaged DNA molecule to its original state before the break occurred. However, during meiosis, the process facilitates chromosomal crossover. This is when regions of similar but not identical DNA are exchanged between homologous chromosomes. This exchange creates new combinations of genes. These combinations represent genetic variation in offspring, which allows populations to adapt through evolution.

Double-strand break repair models that act via homologous recombination
Double-strand break repair models that act via homologous recombination

Scientists have mapped the history of this discovery over many decades. In the early 1900s, William Bateson and Reginald Punnett found that certain genes are genetically linked and do not assort independently. In 1911, Thomas Hunt Morgan suggested that "crossovers" could occur between these linked genes. Later, Barbara McClintock and Harriet Creighton demonstrated that chromosomal crossover actually happens during meiosis. In 1947, Joshua Lederberg discovered that bacteria also undergo genetic recombination. This was a major finding because bacteria were previously thought to reproduce only through asexual binary fission. Lederberg later won the 1958 Nobel Prize for this work.

Morgan crossover 1
Morgan crossover 1

Further breakthroughs led to modern genetic engineering. In 1964, Robin Holliday proposed a model for recombination that included the exchange of material through Holliday junctions. In 1983, Jack Szostak and his colleagues presented the DSBR pathway model. These models helped researchers understand how to use gene targeting to introduce specific genetic changes. For their work in developing gene targeting techniques, Mario Capecchi, Martin Evans, and Oliver Smithies were awarded the 2007 Nobel Prize in Physiology or Medicine. This technology allows scientists to manipulate the genomes of target organisms with high precision.

The timing of this process is strictly regulated by the cell cycle. Homologous recombination primarily occurs during the S and G2 phases. During these phases, sister chromatids are available to act as templates. Sister chromatids are ideal because they are identical copies of a given chromosome. In contrast, other repair methods like non-homologous end joining (NHEJ) are more common during the G1 phase. NHEJ is a different mechanism that does not require a long homologous sequence to guide the repair.

Cell Cycle 2
Cell Cycle 2

In eukaryotes, the process is also influenced by the structure of chromatin. Chromatin is how DNA is packaged within the cell. For repair to happen, the chromatin must undergo remodeling to allow enzymes to reach the DNA. This process happens very quickly. For example, the protein PARP1 can appear at damage sites in less than one second. Within 10 seconds, a chromatin remodeler called Alc1 can arrive to help relax the chromatin. This rapid response ensures that the DNA repair machinery can access the broken strands as quickly as possible. This complex coordination is essential for maintaining the stability of the genome.

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🖼️ Images & Media (12)
File:HR in meiosis.svg
HR in meiosis.svg
File:Morgan crossover 1.jpg
Morgan crossover 1.jpg
File:Cell Cycle 2.svg
Cell Cycle 2.svg
File:Double-strand break repair models that act via homologous recombination.png
Double-strand break repair models that...
File:HR schematic diagram.svg
HR schematic diagram.svg
File:SingleStrandAnnealing animated.svg
SingleStrandAnnealing animated.svg
File:Homologous recombination 3cmt.png
Homologous recombination 3cmt.png
File:HR RecBCD RecA.svg
HR RecBCD RecA.svg
File:S2m structure of SARS-CoV.png
S2m structure of SARS-CoV.png
File:Joining of single-ended double strand breaks could lead to rearrangements.png
Joining of single-ended double strand...
File:HR proteins conserved domains.svg
HR proteins conserved domains.svg
File:ChimericMouseWithPups.jpg
ChimericMouseWithPups.jpg
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