Microtubules and Alp7–Alp14 (TACC–TOG) reposition chromosomes before meiotic segregation

Abstract

Tethering kinetochores at spindle poles facilitates their efficient capture and segregation by microtubules at mitotic onset in yeast. During meiotic prophase of fission yeast, however, kinetochores are detached from the poles, which facilitates meiotic recombination but may cause a risk of chromosome mis-segregation during meiosis. How cells circumvent this dilemma remains unclear. Here we show that an extensive microtubule array assembles from the poles at meiosis I onset and retrieves scattered kinetochores towards the poles to prevent chromosome drift. Moreover, the microtubule-associated protein complex Alp7-Alp14 (the fission yeast orthologues of mammalian TACC-TOG) is phosphorylated by Polo kinase, which promotes its meiosis-specific association to the outer kinetochore complex Nuf2-Ndc80 of scattered kinetochores, thereby assisting in capturing remote kinetochores. Although TOG was recently characterized as a microtubule polymerase, Dis1 (the other TOG orthologue in fission yeast), together with the Dam1 complex, plays a role in microtubule shortening to pull kinetochores polewards. Thus, microtubules and their binding proteins uniquely reconstitute chromosome configuration during meiosis.

The Kinetochore Protein Kis1/Eic1/Mis19 Ensures the Integrity of Mitotic Spindles through Maintenance of Kinetochore Factors Mis6/CENP-I and CENP-A

“…The latter strain appeared suitable for use in combination with severe mutation backgrounds that affect microtubule formation because the former GFP-Atb2 construct occasionally showed synthetic growth defects when combined with some mutations. Strain Z2-GFP-Atb2 has been used to elucidate previously unknown microtubule behaviors in various aspects of mitosis [26] and meiosis [27], [28], [29], [30]. We therefore prepared a three-colored strain expressing GFP-Atb2, Nup40-mCherry [31], and Sfi1-CFP (cyan fluorescent protein) [32] to monitor the behavior of microtubules, the nuclear envelope, and the SPB, respectively ( Figure 1A ).…”

Meiotic nuclear movements in fission yeast are regulated by the transcription factor Mei4 downstream of a Cds1‐dependent replication checkpoint pathway

“…A possible explanation for CDK-mediated abortion of nuclear movements is that cytoplasmic microtubules are reorganized to spindle microtubules upon entry to nuclear divisions (Kakui et al . 2013). …”

“…This difference indicates that Mei4 terminates nuclear movements in the horsetail stage, whereas CDK aborts nuclear movements by driving nuclear divisions. A possible explanation for CDK-mediated abortion of nuclear movements is that cytoplasmic microtubules are reorganized to spindle microtubules upon entry to nuclear divisions (Kakui et al 2013). When the Cds1-dependent replication checkpoint is activated, Cdc25 overproduction is not sufficient for the abortion of nuclear movements, and Mik1/ Wee1 inactivation is required, suggesting that Mik1/Wee1 dominates the counteractive Cdc25.…”

An unconventional interaction between Dis1/TOG and Mal3/EB1 in fission yeast promotes the fidelity of chromosome segregation

“…These two proteins share essential functions; each single deletion mutant is viable, whereas double deletions are inviable (Aoki et al, 2006; Garcia et al, 2002; Hsu and Toda, 2011; Kakui et al, 2013; Nabeshima et al, 1995; Nakaseko et al, 2001). Whereas Alp14 has been shown to be a MT polymerase like other family members (Al-Bassam et al, 2012; Hussmann et al, 2016), a biochemical characterisation of the catalytic properties of Dis1 at MT ends has not yet been performed.…”