The nuclear lamina is essential to protect genome integrity from mechanical stress. This requirement is more stringent in some tissues and developmental events. During oogenesis, meiotic nuclei are situated in a stressful environment filled with cytoskeletons. The nuclear lamina, consisting of the lamin proteins, is a conserved component of the nuclear envelope that can confer mechanical rigidity to the meiotic nuclei. C.elegans expresses a single lamin protein, LMN-1, which is similar to mammalian B-type lamin. Loss of LMN-1 results in near-complete sterility, with hypercondensed chromatin observed in many germline nuclei. The exact functions of LMN-1 in meiotic nuclei during oogenesis, however, remains unclear. Using the auxin-inducible degradation system, we found that acute depletion of LMN-1 in C.elegans germline recapitulated nuclear collapse seen in lmn-1 homozygotes during late stages of meiotic prophase. LMN-1 depletion also led to persistent DNA double strand breaks and elevated apoptosis, but germline apoptosis is neither sufficient nor required for nuclear collapse. We further observed prolonged and excessive clustering of the LINC complex proteins SUN-1 and ZYG-12 at the nuclear envelope (NE) upon LMN-1 acute depletion. Importantly, co-depletion of SUN-1 or ZYG-12, or inhibition of dynein-mediated forces, rescued the nuclear collapse triggered by acute LMN-1 depletion. By contrast, co-depletion of the inner nuclear membrane proteins EMR-1/LEM-2 or SAMP-1 rendered nuclei susceptible to collapse even earlier, at the time of meiotic entry. Live imaging demonstrated that shrinkage of the NE preceded chromosome hypercondensation during nuclear collapse, and that before NE shrinkage happened, LINC complex asymmetrically redistribute to one side of the NE in a dynein-dependent manner. Finally, the connection between the pairing center regions of the chromosomes and the NE, albeit being important for LINC complex function during homolog pairing, is dispensable for nuclear collapse caused by LMN-1 depletion. Together our results suggest that lamin cooperates with additional inner nuclear membrane proteins to protect meiotic nuclei from collapse by antagonizing forces exerted by dynein and transmitted through the LINC complex during oogenesis. Our work has also established an inducible system for modeling laminopathy.

Affiliations:
- Department of Genome Sciences, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA
- Howard Hughes Medical Institute, Chevy Chase, MD
- University of California Berkeley, Berkeley, CA