PT  - JOURNAL ARTICLE
AU  - Cori K. Cahoon
AU  - G. Matthew Heenan
AU  - Zulin Yu
AU  - Jay R. Unruh
AU  - Sean McKinney
AU  - R. Scott Hawley
TI  - Synaptonemal complex architecture facilitates the chromosome-specific regulation of recombination in Drosophila
AID  - 10.1101/277764
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 277764
4099  - http://biorxiv.org/content/early/2018/03/06/277764.short
4100  - http://biorxiv.org/content/early/2018/03/06/277764.full
AB  - In Drosophila, meiotic recombination is initiated by the formation of programmed DNA double-strand breaks (DSBs), which occur within the context of the synaptonemal complex (SC). To better understand the role of the SC in mediating recombination we created an in-frame deletion mutant in c(3)G (deleting amino acids L340 to N550, denoted as c(3)GccΔ1), which encodes the major transverse filament protein of the SC. Although c(3)GccΔ1 oocytes assemble ribbon-like SC and exhibit normal DSB formation, the euchromatic SC precociously disassembles into fragments that persist until mid to late pachytene in both c(3)GccΔ1 heterozygotes and homozygotes. Centromeric SC, however, is unaffected in both genotypes. Thus, c(3)GccΔ1 is a separation-of-function mutant that establishes different functional and structural requirements between euchromatic and centromeric SC. Our data also demonstrate that the chromosome arms differ in their sensitivity to c(3)GccΔ1-induced perturbations in the SC. The X chromosome is distinctly sensitive to these perturbations, such that euchromatic pairing and crossing over are altered in c(3)GccΔ1 heterozygotes and severely reduced in c(3)GccΔ1 homozygotes. On the autosomes, crossovers are shifted to centromere-proximal regions and crossover interference is defective in both c(3)GccΔ1 homozygotes and heterozygotes. However, only c(3)GccΔ1 homozygotes display a progressive loss of euchromatic pairing in distal autosomal regions, suggesting that discontinuity in the euchromatic SC—rather than failed pairing—might cause the altered crossover distribution. These phenotypes reveal that different chromatin states or regions have differing requirements to maintain both the SC and homologous pairing. Furthermore, c(3)GccΔ1 is the first mutant in Drosophila to demonstrate that the SC appears to facilitate the regulation of recombination frequency and distribution differently on each chromosome.Author Summary Chromosome segregation errors during meiosis are the leading cause of miscarriage and birth defects in humans. To prevent these errors from occurring, meiotic cells have evolved multiple mechanisms to ensure that each gamete receives exactly half the number of chromosomes. During meiosis I, this is accomplished by forming a crossover between homologous chromosomes, which is facilitated by a large protein complex called the synaptonemal complex (SC). The SC is assembled between homologous chromosomes during early prophase I, and it is unclear how the SC regulates the position and number of crossovers each homolog receives. To better understand the role of the SC in mediating recombination, we created an in-frame deletion mutant in Drosophila melanogaster in the gene encoding the C(3)G protein, the major transverse filament protein of the SC. Although mutant oocytes assemble ribbon-like SC, the SC along the chromosome arms precociously disassembles in early meiosis. Surprisingly, the SC around the centromeres is unaffected in these mutants, suggesting that the requirements for SC formation may differ depending on where the SC is located along the chromosomes. Our data also demonstrate that the chromosome arms differ in their sensitivity to the mutant-induced perturbations of the SC in both crossing over and homolog pairing.