Department of Molecular Life Science (DMLS), University of Zurich, Zurich, Switzerland.
PLoS Genet. 2022 Jul 27;18(7):e1010327. doi: 10.1371/journal.pgen.1010327. eCollection 2022 Jul.
The bivalent chromosomes that are generated during prophase of meiosis I comprise a pair of homologous chromosomes. Homolog pairing during prophase I must include mechanisms that avoid or eliminate entanglements between non-homologous chromosomes. In Drosophila spermatocytes, non-homologous associations are disrupted by chromosome territory formation, while linkages between homologous chromosomes are maintained by special conjunction proteins. These proteins function as alternative for crossovers that link homologs during canonical meiosis but are absent during the achiasmate Drosophila male meiosis. How and where within bivalents the alternative homolog conjunction proteins function is still poorly understood. To clarify the rules that govern territory formation and alternative homolog conjunction, we have analyzed spermatocytes with chromosomal aberrations. We examined territory formation after acute chromosome cleavage by Cas9, targeted to the dodeca satellite adjacent to the centromere of chromosome 3 specifically in spermatocytes. Moreover, we studied territory organization, as well as the eventual orientation of chromosomes during meiosis I, in spermatocytes with stable structural aberrations, including heterozygous reciprocal autosomal translocations. Our observations indicate that alternative homolog conjunction is applied in a spatially confined manner. Comparable to crossovers, only a single conjunction spot per chromosome arm appears to be applied usually. These conjunction spots resist separation by the dispersing forces that drive apart homologous pericentromeric heterochromatin and embedded centromeres within territories, as well as the distinct chromosomal entities into peripheral, maximally separated territories within the spermatocyte nucleus.
在减数分裂前期 I 生成的二价染色体由一对同源染色体组成。在前期 I 中，同源配对必须包括避免或消除非同源染色体缠绕的机制。在果蝇精母细胞中，非同源染色体的关联被染色体区室形成破坏，而同源染色体之间的连接则由特殊的连接蛋白维持。这些蛋白质作为在经典减数分裂中连接同源染色体的交叉的替代物发挥作用，但在非联会的果蝇雄性减数分裂中缺失。替代同源连接蛋白在二价体中如何以及在何处发挥作用仍然知之甚少。为了阐明控制区室形成和替代同源连接的规则，我们分析了具有染色体畸变的精母细胞。我们通过 Cas9 急性染色体切割分析了染色体畸变后 3 号染色体着丝粒附近的十二面体卫星处的特定精母细胞中的域形成。此外，我们研究了在具有稳定结构畸变的精母细胞中的域组织，以及减数分裂 I 中染色体的最终取向，包括杂合相互易位。我们的观察表明，替代同源连接是以空间受限的方式应用的。与交叉类似，每个染色体臂似乎只应用一个单一的连接点。这些连接点抵抗分离力的作用，这种分离力会将同源着丝粒异染色质和嵌入的着丝粒分开，并将不同的染色体实体分开到精母细胞核中的外围、最大分离的域中。
