Other meganucleases

HO

HO was the first identified natural meganucleases. HO initiates mating type switching in baker’s yeast.

The baker’s yeast Saccharomyces cerevisiae can be haploid or diploid. Yeast of opposite mating types, a and alpha, can mate to produce a diploid cell. Diploids can sporulate, resulting in four haploid spores, two spores with an a mating type, and two alpha spores. However, wild-type haploids can switch their mating type at each cell cycle, by a finely regulated process of DSB-induced gene conversion. The transcriptionally active MAT locus, coding for the mating type is cut by HO, and uses either of two transcriptionally inactive cassettes as homologous donor template, to result in a MATa or MATalpha locus.

HO is an atypical LAGLIDADG protein, with a zinc finger domain in its COOH-terminal part, and a very complex transcriptional and posttranslational regulation. Although HO has not been used in a large variety of organisms, HO-induced DSB repair has been studied extensively in yeast, and a very large part of our current knowledge of DSB repair is based on these studies.

I-CreI

I-CreI is a LAGLIDADG protein from the Chlamydomonas reinhardti algae. Although it has been rarely used for genome engineering, structural studies make it a paradigm for the study of DNA cleavage by homing endonucleases. I-CreI was the first LAGLIDADG protein to be crystallized with its DNA target.

I-TevI

I-TevI is a GIY-YIG protein from T4 phages. The biology and biochemistry of I-TevI are better characterized than that of any other homing endonuclease, I-SceI and HO excepted. Early studies showed that similar to I-SceI and HO, I-TevI was capable of promoting DSB-induced gene conversion.