Meiotic Pairing and Disjunction of Mini-X Chromosomes in Drosophila Is Mediated by 240-bp rDNA Repeats and the Homolog Conjunction Proteins SNM and MNM

Abstract

In most eukaryotes, segregation of homologous chromosomes during meiosis is dependent on crossovers that occur while the homologs are intimately paired during early prophase. Crossovers generate homolog connectors known as chiasmata that are stabilized by cohesion between sister-chromatid arms. In Drosophila males, homologs pair and segregate without recombining or forming chiasmata. Stable pairing of homologs is dependent on two proteins, SNM and MNM, that associate with chromosomes throughout meiosis I until their removal at anaphase I. SNM and MNM localize to the rDNA region of the X-Y pair, which contains 240-bp repeats that have previously been shown to function as cis-acting chromosome pairing/segregation sites. Here we show that heterochromatic mini-X chromosomes lacking native rDNA but carrying transgenic 240-bp repeat arrays segregate preferentially from full-length sex chromosomes and from each other. Mini-X pairs do not form autonomous bivalents but do associate at high frequency with the X-Y bivalent to form trivalents and quadrivalents. Both disjunction of mini-X pairs and multivalent formation are dependent on the presence of SNM and MNM. These results imply that 240-bp repeats function to mediate association of sex chromosomes with SNM and MNM. P AIRING of homologous chromosomes is an essential step in meiosis, setting the stage for the segregation of homologs to opposite poles (Page and Hawley 2003;McKee 2004). In most eukaryotes, pairing is accompanied by high frequencies of recombination and by formation of synaptonemal complexes, proteinaceous structures that connect homologs from end to end during the pachytene stage of meiotic prophase. Segregation of homologs requires not only that they pair but also that they undergo at least one crossover. Crossovers generate cytologically visible linkers known as chiasmata, which are essential to maintaining bivalent integrity throughout late prophase I and metaphase I (Hawley 1988).However, synaptonemal complexes, crossing over, and chiasmata are not universal prerequisites for meiotic chromosome segregation. Achiasmate segregation, i.e., segregation of homologs without chiasmata, is found in one sex or the other in several groups of eukaryotes (Wolf 1994). In Drosophila male meiosis, crossing over is normally completely absent and the homologs fail to form either synaptonemal complexes or chiasmata, yet homologs are stably conjoined during late prophase I and metaphase I and segregate from one another with great regularity during anaphase I.Recent data show that stable conjunction and accurate segregation of all four homolog pairs in Drosophila male meiosis depends upon two proteins: stromalin in meiosis (SNM), a homolog of the SCC3/SA cohesin proteins, and Mod(mdg4) in meiosis (MNM), a BTB domain protein (Thomas et al. 2005). SNM and MNM colocalize to meiotic chromosomes throughout prophase I and metaphase I but disappear at the onset of anaphase I, suggesting that they function directly in stabilization of pairing, i.e., as substitutes for ch...

Meiosis in male Drosophila

“…Deletion of the X chromosome rDNA abolishes localization to the X but not to the Y, and X localization is restored by transgenes carrying 240 bp repeat arrays. SNM and MNM also localize to transgenes containing arrays of 240 bp repeats inserted on mini-X chromosomes where they promote conjunction and segregation of pairs of such minichromosomes from each other 74 . This shows that 240 bp repeats function to recruit SNM and MNM to sex chromosomes and that they must be present on both homologs to mediate conjunction and segregation.…”

Homologous pairing and the role of pairing centers in meiosis

“…3B) (Thomas et al, 2005). Moreover, localization of SNM and MNM to the X chromosome is lost when the rDNA genes are deleted, but restored when transgenic 240-bp repeat arrays are inserted (Thomas et al, 2005;Thomas and McKee, 2007). These findings indicate that the 240-bp repeats function to recruit the SNM-MNM complex to the sex chromosomes.…”

A specific family of interspersed repeats (SINEs) facilitates meiotic synapsis in mammals

“…Nevertheless, while we cannot be certain of the specific mechanism by which SINES interact with the SC, our results provide evidence of a new meiotic function for repetitive elements. From studies of multiple organisms, it is clear that repetitive sequences are important in the earliest events of meiotic prophase; e.g., telomeric repeats facilitate homolog interactions by formation of the meiotic bouquet [19-27], and studies of C. elegans [28] and Drosophila [29], among others, implicate other specific repetitive elements in the pairing process. However, little has been known of the possible contribution of specific DNA sequences to the formation of the synaptonemal complex in mammals.…”