Karyogamy, the process of nuclear fusion is required for two haploid gamete nuclei to form a zygote. Also, in haplobiontic organisms, karyogamy is required to produce the diploid nucleus/cell that then enters meiosis. We identify sun like protein 1 (Slp1), member of the mid-Sad1p, UNC-84-domain ubiquitous family, as essential for karyogamy in the filamentous fungus Sordaria macrospora, thus uncovering a new function for this protein family. Slp1 is required at the last step, nuclear fusion, not for earlier events including nuclear movements, recognition, and juxtaposition. Correspondingly, like other family members, Slp1 localizes to the endoplasmic reticulum and also to its extensions comprising the nuclear envelope. Remarkably, despite the absence of nuclear fusion in the slp1 null mutant, meiosis proceeds efficiently in the two haploid "twin" nuclei, by the same program and timing as in diploid nuclei with a single dramatic exception: the normal prophase program of recombination and synapsis between homologous chromosomes, including loading of recombination and synaptonemal complex proteins, occurs instead between sister chromatids. Moreover, the numbers of recombinationinitiating double-strand breaks (DSBs) and ensuing recombinational interactions, including foci of the essential crossover factor Homo sapiens enhancer of invasion 10 (Hei10), occur at half the diploid level in each haploid nucleus, implying per-chromosome specification of DSB formation. Further, the distribution of Hei10 foci shows interference like in diploid meiosis. Centromere and spindle dynamics, however, still occur in the diploid mode during the two meiotic divisions. These observations imply that the prophase program senses absence of karyogamy and/or absence of a homolog partner and adjusts the interchromosomal interaction program accordingly.sisters versus homologs | recombination/synapsis K aryogamy is the process by which two nuclei fuse to produce a single nucleus. This process is critical in diploid organisms (e.g., mammals and plants) when haploid egg and sperm nuclei fuse to produce a diploid nucleus and zygote. In organisms with a haploid vegetative cycle (e.g., fungi and most algae), karyogamy is required to produce the diploid nucleus/cell, which will then enter meiosis. In both situations, karyogamy involves two steps: nuclear movement leading to nuclear juxtaposition (congression) and final fusion of the nuclear membranes. Cooperation of the cytoskeleton components is required for nuclear movement and correct positioning of the nuclei (e.g., ref. 1).In budding yeast, premeiotic karyogamy requires several genes (named Kar1 to Kar9) with their mutant defects corresponding to two steps: nuclear congression, which involves cytoskeleton components, motor proteins and the spindle pole body (SPB, mammal centrosome equivalent) and fusion of the two haploid nuclear envelopes (NEs), which involves either the endoplasmic reticulum (ER) per se or protein translocation into the perinuclear space (reviewed in refs. 2-4 and references t...