Studies on the Mechanisms of Homolog Pairing and Sister Chromatid Cohesion During Drosophila Male Meiosis

Meiosis is a complex process involving one round of DNA replication followed by two rounds of cell divisions. The proper segregation of homologs at meiosis I and sister chromatids during meiosis II is essential for the survival of the offspring. Aberrant chromosome segregation at any stage of meiosis can lead to aneuploidy. Meiotic chromosome segregation without crossing over or chiasmata is a widespread but poorly understand chromosome segregation pathway. In male Drosophila meiosis the absence of recombination in chromosomes makes it easier to identify mutations which influence homologous chromosome pairing and segregation. Modifier of Mdg4 in Meiosis (MNM), a protein encoded by modifier of mdg4, is required for integrity of chromosome territories and stability of achiasmatic bivalents and for normal homolog segregation in male Drosophila meiosis I. MNM localizes to clusters of nucleolar and autosomal foci during meiotic prophase I (PI) and to a novel, compact structure associated with the X-Y bivalent during prometaphase I (PMI) and metaphase I (MI). Stromalin in Meiosis (SNM), a member of the SCC3/STAG cohesion family, is required for homolog pairing in male Drosophila but not for meiotic sister chromatid cohesin. SNM protein co-localizes with MNM to the nucleolus throughout PI and to a prominent focus on the X-Y bivalent during PMI and MI. Mutations of snm and mnm exhibit similar homolog pairing failure during meiosis I. Consequently we used the Yeast Two-Hybrid System to determine whether SNM and MNM can interact with each other. We concluded that MNM can interact with itself and SNM. We also found that SNM interacts with the BTB domain of MNM and that the FLYWCH domain in the C-terminus of the MNM protein may play a role in the interaction between MNM and SNM. Sister chromatid cohesion (SCC) is required for proper chromosome segregation during mitosis and meiosis. The protein complex cohesin is a major component of SCC and links sister chromatids together from the time of their replication until their segregation. sisters unbound (sun) is a novel gene required in male and female Drosophila for meiotic SCC. Mutations in sun cause premature sister chromatid segregation (PSCS) and nondisjunction (NDJ) of both homologous and sister chromatids, and also disrupt normal recombination and synapsis in female meiosis. The four chromatids in each bivalent exhibit random segregation at meiosis I. We found that centromeric cohesion is lost in the absence of SUN during mid-prophase (S4). Surprisingly, cytological analysis shows chromosome behavior appears relatively normal during meiosis I. Double mutations sun snm and sun mnm impair the integrity of chromosome territories. In addition we found that SNM, but not MNM, is required for centromere pairing in mid-prophase (S3) and simultaneous loss of SNM and SUN proteins causes PSCS at mid-prophase I (S3), which is earlier than in single mutants in snm or sun. These findings indicated that these two proteins play complementary roles in meiotic cohesion