Chromosome architecture and homologous recombination in meiosis

Abstract

Meiocytes organize higher-order chromosome structures comprising arrays of chromatin loops organized at their bases by linear axes. As meiotic prophase progresses, the axes of homologous chromosomes align and synapse along their lengths to form ladder-like structures called synaptonemal complexes (SCs). The entire process of meiotic recombination, from initiation via programmed DNA double-strand breaks (DSBs) to completion of DSB repair with crossover or non-crossover outcomes, occurs in the context of chromosome axes and SCs. These meiosis-specific chromosome structures provide specialized environments for the regulation of DSB formation and crossing over. In this review, we summarize insights into the importance of chromosome architecture in the regulation of meiotic recombination, focusing on cohesin-mediated axis formation, DSB regulation via tethered loop-axis complexes, inter-homolog template bias facilitated by axial proteins, and crossover regulation in the context of the SCs. We also discuss emerging evidence that the SUMO and the ubiquitin-proteasome system function in the organization of chromosome structure and regulation of meiotic recombination.

Keywords: axis-loop structure; cohesin; crossover; meiotic recombination; synaptonemal complex.

FIGURE 1

Axis-loop chromosome structure and the synaptonemal complex in mice (A) Surface spreads of mouse oocyte pachytene chromosomes immunostained for RAD21L (green), SYCP3 (magenta), and DNA (DAPI; blue). DNA is condensed on chromosome axes where cohesin complexes and axis core proteins localize and spread as loops from axes. RAD21L and SYCP3 are shown as a representative of meiotic cohesin and axis core protein, respectively (B) Schematic representation of the mouse synaptonemal complex. Cohesin complexes interconnect axes of sister chromatids and lateral elements SYCP2 and SYCP3 and a transverse filament protein SYCP1 form a ladder/zipper-like structure.

FIGURE 2

Tethered loop-axis complex (TLAC) formation to regulate DSB formation in budding yeast. Schematic representation of the budding yeast TLAC. Spo11 partner Rec114-Mer2-Mei4 complex localizes to chromosome axes where Rec8 cohesin and an axial element Red1 reside, and Spp1, a component of the Set1/COMPASS complex, tethers Spo11-bound DSB hotspots within loops to chromosome axes via the interaction with Mer2.

FIGURE 3

Chromosomal localization of RNF212 and HEI10 in mice. Successive stages of mouse pachytene spermatocytes immunostained for RNF212 (green), HEI10 (magenta), and SYCP3 (blue), HEI10 and SYCP3. RNF212 forms numerous discrete foci along the entire SCs (marked by SYCP3) in early pachynema before HEI10 foci emerge (top), loses most of foci but accumulates at HEI10-bound crossover sites in mid pachynema (middle), and eventually is restricted to crossover sites in late pachynema (bottom).

FIGURE 4

Chromosome axes decorated by SUMO and Ubiquitin in mice. Surface spreads of mouse spermatocyte chromosomes immunostained for SYCP3 (green) and SUMO2/3 (green; top) and Ubiquitin (green; bottom), respectively. Both SUMO and ubiquitin are enriched on chromosome axes where SYCP3 localizes.