Transient and Partial Nuclear Lamina Disruption Promotes Chromosome Movement in Early Meiotic Prophase

Abstract

SummaryMeiotic chromosome movement is important for the pairwise alignment of homologous chromosomes, which is required for correct chromosome segregation. Movement is driven by cytoplasmic forces, transmitted to chromosome ends by nuclear membrane-spanning proteins. In animal cells, lamins form a prominent scaffold at the nuclear periphery, yet the role lamins play in meiotic chromosome movement is unclear. We show that chromosome movement correlates with reduced lamin association with the nuclear rim, which requires lamin phosphorylation at sites analogous to those that open lamina network crosslinks in mitosis. Failure to remodel the lamina results in delayed meiotic entry, altered chromatin organization, unpaired or interlocked chromosomes, and slowed chromosome movement. The remodeling kinases are delivered to lamins via chromosome ends coupled to the nuclear envelope, potentially enabling crosstalk between the lamina and chromosomal events. Thus, opening the lamina network plays a role in modulating contacts between chromosomes and the nuclear periphery during meiosis.

The tumor suppressor BRCA1-BARD1 complex localizes to the synaptonemal complex and regulates recombination under meiotic dysfunction in Caenorhabditis elegans

“…elegans BRC-1 may be uniquely required for nuclear localization or retention, and in its absence BRD-1 cannot enter or be retained in the nucleus. The weak nucleoplasmic BRD-1 signal observed at the end of meiotic prophase in the absence of BRC-1 most likely reflects differences in the nuclear membrane as oogenesis proceeds [ 90 , 91 ].…”

Meiotic chromosome movement: what’s lamin got to do with it?

“…When the lamina crosslinking (and thus its rigidity) is artificially maintained, as in the [gfp::lmn-1 8A ] mutant, chromosome movements are slower. By measuring the ability of chromosomes to diffuse along the nuclear envelope (by preventing force transmission through the cytoplasm), we confirmed that the more rigid lamina in [gfp::lmn-1 8A ] restricts chromosome end diffusion [27]. The failure to fully abrogate chromosome movement in the [gfp::lmn-1 8A ] mutant could be explained by the cytoskeletal forces being strong enough to overcome hindrance by the more rigid lamina.…”

“…However, we suspect that lamina rigidity is also mediated by many other lamina-and nuclear envelope-associated proteins, and therefore that lamina remodeling might be a multifactorial process. Although the lamina clearly persists for longer in mitotic cell divisions in the mutant [27], it is striking that lamina disassembly is not a rate-limiting step for nuclear envelope breakdown.…”

“…As the rigid lamina network resides between chromatin and the nuclear envelope, it would be well placed to inhibit chromosome movements and their connections with the nuclear envelope. In our recent study, we investigated whether and how the nuclear lamina is remodeled in the C. elegans germline, particularly during the leptotene/zygotene stages of prophase I, where RPMs take place [27].…”

Comparing and Contrasting the Effects of Drosophila Condensin II Subunit dCAP-D3 Overexpression and Depletion in Vivo

“…As the ∆25 allele is a second chromosome deletion that results in the loss of 63 other genes and regulatory RNAs in addition to dCap-D3 , including the B-type lamin lamDm0 , it is possible that decreased expression of these other factors could influence mitotic progression, thus skewing the prophase timing results. Indeed, the nuclear lamina has been shown to be important for regulating chromosome movement during meiotic prophase in Caenorhabditis elegans ( Link et al 2018 ), but whether it plays similar roles in mitotic cells is unknown.…”