RT Journal Article SR Electronic T1 The yeast mating-type switching endonuclease HO is a domesticated member of an unorthodox homing genetic element family JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.01.20.913210 DO 10.1101/2020.01.20.913210 A1 Aisling Y. Coughlan A1 Lisa Lombardi A1 Stephanie Braun-Galleani A1 Alexandre A. R. Martos A1 Virginie Galeote A1 Frédéric Bigey A1 Sylvie Dequin A1 Kevin P. Byrne A1 Kenneth H. Wolfe YR 2020 UL http://biorxiv.org/content/early/2020/01/21/2020.01.20.913210.abstract AB The mating-type switching endonuclease HO plays a central role in the natural life cycle of Saccharomyces cerevisiae, but its evolutionary origin is unknown. HO is a recent addition to yeast genomes, present in only a few genera. It resembles a degenerated intein fused to a zinc finger domain. Here we show that HO is structurally and phylogenetically related to a family of unorthodox homing genetic elements found in Torulaspora and Lachancea yeasts. These WHO elements integrate into the aldolase gene FBA1, replacing its 3’ end each time. Their structural organization is different from all known classes of homing elements. We show that a WHO protein cleaves Torulaspora delbrueckii FBA1 efficiently and in an allele-specific manner, leading to DNA repair by gene conversion or NHEJ. The DNA rearrangement steps during WHO element homing are very similar to those during mating-type switching, and indicate that HO is a domesticated WHO-like element.