The Nucleoporin Nup2 Contains a Meiotic-Autonomous Region that Promotes the Dynamic Chromosome Events of Meiosis

Abstract

Meiosis is a specialized cellular program required to create haploid gametes from diploid parent cells. Homologous chromosomes pair, synapse, and recombine in a dynamic environment that accommodates gross chromosome reorganization and significant chromosome motion, which are critical for normal chromosome segregation. In Saccharomyces cerevisiae, Ndj1 is a meiotic telomere-associated protein required for physically attaching telomeres to proteins embedded in the nuclear envelope. In this study, we identified additional proteins that act at the nuclear periphery from meiotic cell extracts, including Nup2, a nonessential nucleoporin with a known role in tethering interstitial chromosomal loci to the nuclear pore complex. We found that deleting NUP2 affects meiotic progression and spore viability, and gives increased levels of recombination intermediates and products. We identified a previously uncharacterized 125 aa region of Nup2 that is necessary and sufficient for its meiotic function, thus behaving as a meiotic autonomous region (MAR). Nup2-MAR forms distinct foci on spread meiotic chromosomes, with a subset overlapping with Ndj1 foci. Localization of Nup2-MAR to meiotic chromosomes does not require Ndj1, nor does Ndj1 localization require Nup2, suggesting these proteins function in different pathways, and their interaction is weak or indirect. Instead, several severe synthetic phenotypes are associated with the nup2D ndj1D double mutant, including delayed turnover of recombination joint molecules, and a failure to undergo nuclear divisions without also arresting the meiotic program. These data suggest Nup2 and Ndj1 support partially overlapping functions that promote two different levels of meiotic chromosome organization necessary to withstand a dynamic stage of the eukaryotic life cycle.

Persistent DNA-break potential near telomeres increases initiation of meiotic recombination on short chromosomes

“…However, the interpretation of these results is complicated by the fact that loss of NDJ1 also causes synapsis defects 53 . As the nonessential nucleoporin Nup2 was recently identified as an interactor of Ndj1 54 , we also analyzed Hop1 in nup2Δ mutants. Intriguingly, Hop1 did not become enriched in the EARs in late prophase in nup2Δ ndt80Δ mutants (Fig.…”

Meiotic cellular rejuvenation is coupled to nuclear remodeling in budding yeast

“…The nuclear basket nucleoporins Nup1 and Nup60 have innate membrane binding and shaping capabilities, making them attractive candidates to initiate insertion of new NPCs (Mészáros et al, 2015). Indeed, deletion of non-essential nuclear basket nucleoporins results in reduced sporulation efficiency and impaired gamete viability, supporting an important functional role during the meiotic program (Chu et al, 2017).…”

The dynamic three-dimensional organization of the diploid yeast genome

“…Indeed, the presence of paired HAS1-TDA1 alleles in the nucleoplasm suggests that such nuclear pore-independent pairing mechanisms may act at HAS1-TDA1 ( Figure 5C and Figure 5—source data 2 ). Interestingly, a recent study showed that Nup2 is involved in meiotic homolog pairing ( Chu et al, 2017 ), suggesting that Nup2 may more generally play a role in homolog pairing.…”