Crucial Genetic Diversity Enzyme Long Sought By Biologists Discovered By Scientists At The Scripps Research Institute

In the current issues of the journals Cell and Molecular Cell, the researchers have published papers that describe Mus81, a resolvase enzyme of the fission yeast Schizosaccharomyces pombe, and its human analog.

Resolvase is essential for a crucial step in DNA recombination, says Russell, because it is the molecule that allows two chromosomes to cross over. "It is one of the most important enzymes involved in genetic recombination," he says.

Genetic recombination occurs in the process of meiosis, when chromosomes from the mother and father become paired. The aligned chromosomes break and DNA strands from both chromosomes become intertwined at the point of the cross-over. At the molecular level, this combining happens at what is called a "Holliday junction," where the strands of DNA literally cross one another.

However, the DNA must at some point be uncrossed by cutting across the Holliday junction in the last crucial step in genetic recombination. This is the responsibility of resolvase enzymes. The final product of this process is a pair of new chromosomes that have genetic material from both parents.

"[Resolvase] is the molecule that allows children to inherit a unique mixture of traits from mother and father, without it we wouldn't have the infinite range of genetic combinations that makes us all different," says McGowan.

It has long been known that there should be such enzymes, and several examples from other organisms, such as bacteria, have been around for years. And for years, scientists have searched for the resolvase gene in eukaryotic cells, such as humans and yeast, which have linear chromosomes packaged in a nucleus. Until now, none has been found.

Russell and his colleagues showed that Mus81 is an essential component of the resolvase enzyme in yeast cells. Mus81 is structurally unrelated to bacterial resolvases. In a related work, McGowan's study demonstrated that a human analog of the Mus81 protein also has resolvase activity.

The identification of a human resolvase may have a profound effect on cancer therapy because the enzyme also has an important ro