Closed mitosis requires local disassembly of the nuclear envelope

Gautam Dey, Siân Culley, Scott Curran, Ricardo Henriques, Wanda Kukulski, Buzz Baum

Preprint posted on September 23, 2019

What is the mechanism behind closed mitosis in S.pombe? Dey et al. show how a protein named ‘Les1’ ensures the local disassembly of the nuclear envelope on the bridge that connects the two daughter nuclei, thus preventing leakage of nuclear material

Selected by Leeba Ann Chacko

Video depicting the sequence of events during nuclear envelope breakdown in S.pombe cells with and without Les1


Cell division is a fundamental process for life wherein a cell divides into two identical daughter cells. The purpose of cell division is to enable growth, propagation, and replacement of damaged cells. During cell division, cells duplicate their nuclear compartment containing DNA. Mitosis is the process in which these nuclear compartments separate into two independent daughter nuclei.

In most mammalian cells which have open mitosis, one of the key steps in mitosis is the breakdown of the nuclear envelope. However, this is not a universal feature of mitosis among all cells and organisms. Some organisms such as unicellular yeasts are known to undergo ‘closed mitosis’, wherein the nuclear envelope remains intact throughout the cell cycle. Interestingly, as the nucleus divides, it undergoes major shape changes wherein prior to division, it transforms from a spherical to an elongated shape. Correspondingly, after division the nucleus reverts to its spherical shape.

In fission yeast, at the onset of mitosis, the nucleus transforms from a spherical to a dumbbell shape and then constricts to form a thin nuclear bridge between the two daughter nuclei that ultimately split. Interestingly, during this entire process, the nuclear contents remain intact. Dey et al. show that a novel, uncharacterised protein named ‘Les1’ plays a crucial role in keeping the nuclear compartment boundary intact during cell division.

Key findings: 

1) An uncharacterised protein (locus tag SPAC23C4.05c) shows a unique localisation pattern, wherein it forms stalks in the inner surface of the thin nuclear bridge between the two daughter nuclei, during early stages of the bridge formation. As the bridge elongates, Les1 visibly becomes depleted from the mid-zone of the bridge. The authors named the protein ‘Les1’.

2) Since Les1 is localised to the stalks at the midzone, the authors looked at the intersection between the midzone and the stalk of dividing nuclei with the help of electron tomograms. Strikingly, these images show that while the spindle is enveloped by Les1 at the stalks, the midzone region of the spindle is directly projected into the cytoplasm with nothing but a few strands of the endoplasmic reticulum.

3) Two components of the nuclear pore complex (NPC), namely Cut11 and Nup60, show mutually exclusive localisation with respect to Les1. Like what is observed in open mitosis, the NPCs dissociate from the nuclear envelope, thereby leading to its breakdown. The components of the NPC dissociate in a sequential manner with membrane Nups being lost last as the nuclear localisation signal disappears from the midzone. Thus, the steps of local NEB at the midzone of the bridge is similar to NEB in open mitosis.

4) Finally, the authors found that when Les1 is removed, the NPCs are localised across the bridge and as a consequence the bridge is divided in arbitrary locations away from the mid-zone. These random tears in turn lead to leakages in nuclear material from at least one of the two daughter nuclei. Thus, Les1 is required to prevent such leakage from happening.   

What I liked about this preprint: 

I came across this preprint when it was posted on twitter. It was a very interactive post that got me wondering why I never thought about how closed mitosis occurs without affecting the nuclear membrane. I now know that the protein ‘Les1’ restricts NPCs to the mid-zone and thereby prevents leakage from daughter nuclei.

The post also shows how making science easily accessible and interactive can get people to engage in scientific questions that they might never have thought about in the first place.

Questions for the authors: 

1) Do you have any clues on what is preventing the localisation of Les1 throughout the mid-zone region during the later stages of the bridge assembly? Is it possible to visualise Les-1 signal in the absence of NPCs?

2) You have shown that in the absence of Les1, nuclear leakages occur (Figure 4). Do you have any clues on why these leakages are mostly isolated to one of the daughter nuclei?

3) Will you be looking for proteins that are analogous to Les1 in other organisms that undergo closed mitosis? Do you think the mechanism would be similar?


1. Dey, G., Culley, S., Curran, S., Henriques, R., Kukulski, W., & Baum, B. (2019). Closed mitosis requires local disassembly of the nuclear envelope. bioRxiv, 779769.

2. Boettcher, B., & Barral, Y. (n.d.). The cell biology of open and closed mitosis. Nucleus (Austin, Tex.), 4(3), 160–165.

Tags: les1, mitosis, nucleus, s.pombe

Posted on: 3rd February 2020


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