Holliday junction resolvase

Identifiers
EC number	3.1.22.4
CAS number	37211-56-0
Alt. names
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway

Holliday junction resolvase is an enzyme that plays a critical role in the process of genetic recombination. It is responsible for resolving Holliday junctions, which are cruciform structures that form during the exchange of genetic material between homologous DNA molecules. This process is essential for DNA repair, meiosis, and the generation of genetic diversity.

Structure

Holliday junction resolvases are typically small, dimeric proteins that recognize and bind to the four-way junctions in DNA. The structure of these enzymes allows them to introduce symmetrical nicks in the DNA strands, facilitating the resolution of the junction into two separate double-stranded DNA molecules. The active site of the enzyme contains key residues that coordinate the cleavage of the DNA.

Function

The primary function of Holliday junction resolvase is to cleave the DNA at the junction, allowing the recombination process to proceed. This cleavage is precise and occurs at specific sites on the DNA, ensuring that the genetic information is accurately exchanged between the homologous chromosomes. The resolution of Holliday junctions is a critical step in homologous recombination, a process that is vital for the repair of double-strand breaks in DNA.

Mechanism

Holliday junction resolvases operate by introducing nicks in the DNA strands at the junction. The enzyme binds to the junction and induces a conformational change that positions the DNA for cleavage. The cleavage occurs symmetrically, and the enzyme ensures that the strands are cut in a manner that allows for the proper re-ligation of the DNA molecules. This mechanism is highly conserved across different species, highlighting its importance in maintaining genomic stability.

Biological Importance

Holliday junction resolvases are crucial for maintaining the integrity of the genome. By resolving Holliday junctions, these enzymes prevent the accumulation of recombination intermediates that can lead to genomic instability and chromosomal aberrations. In meiosis, the resolution of Holliday junctions is essential for the proper segregation of homologous chromosomes, ensuring the production of viable gametes.

Clinical Significance

Defects in the resolution of Holliday junctions can lead to a variety of genetic disorders. Mutations in the genes encoding Holliday junction resolvases have been associated with increased susceptibility to cancer and other diseases characterized by genomic instability. Understanding the function and regulation of these enzymes is therefore critical for developing therapeutic strategies to address these conditions.

Examples

Several Holliday junction resolvases have been identified in different organisms. In bacteria, the RuvC protein is a well-characterized resolvase that plays a key role in homologous recombination. In eukaryotes, GEN1 and Mus81-Eme1 are examples of resolvases that function in the resolution of Holliday junctions during DNA repair and meiosis.

Research Directions

Ongoing research is focused on elucidating the detailed mechanisms of Holliday junction resolution and the regulation of resolvase activity. Structural studies using techniques such as X-ray crystallography and cryo-electron microscopy are providing insights into the enzyme-DNA interactions and the conformational changes that occur during the resolution process. Additionally, the development of small molecule inhibitors of Holliday junction resolvases is being explored as a potential therapeutic approach for targeting cancer cells with defects in DNA repair pathways.

See Also

• Genetic recombination
• DNA repair
• Meiosis
• Genomic instability

External Links

• [Link to relevant database or resource]