TY - JOUR T1 - Dynein pulling forces on ruptured nuclei counteract lamin-mediated nuclear envelope repair mechanisms in vivo JF - bioRxiv DO - 10.1101/138693 SP - 138693 AU - Lauren Penfield AU - Brian Wysolmerski AU - Reza Farhadifar AU - Michael Martinez AU - Ronald Biggs AU - Hai-Yin Wu AU - Michael Mauro AU - Curtis Broberg AU - Daniel Needleman AU - Shirin Bahmanyar Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/05/30/138693.abstract N2 - Recent work done exclusively in tissue culture cells revealed that the nuclear envelope (NE) undergoes ruptures leading to transient mixing of nuclear and cytoplasmic components. The duration of transient NE ruptures depends on lamins, however the underlying mechanisms and the relevance to in vivo events is not known. Here, we use C. elegans embryos to show that dynein forces that position nuclei increase the severity of lamin-induced NE ruptures in vivo. In the absence of dynein forces, lamin prevents nuclear-cytoplasmic mixing caused by NE ruptures. By monitoring the dynamics of NE rupture events, we demonstrate that lamin is required for a distinct phase in NE recovery that restricts nucleocytoplasmic mixing prior to the full restoration of NE rupture sites. We show that laser-induced puncture of the NE recapitulates phenotypes associated with NE recovery in wild type cells. Surprisingly, we find that embryonic lethality does not correlate with the incidence of NE rupture events suggesting that embryos survive transient losses of NE compartmentalization during early embryogenesis. In addition to presenting the first mechanistic analysis of transient NE ruptures in vivo, this work demonstrates that lamin controls the duration of NE ruptures by opposing dynein forces on ruptured nuclei to allow reestablishment of the NE permeability barrier and subsequent restoration of NE rupture sites. ER -