scholarly journals Cohesins Determine the Attachment Manner of Kinetochores to Spindle Microtubules at Meiosis I in Fission Yeast

2003 ◽  
Vol 23 (11) ◽  
pp. 3965-3973 ◽  
Author(s):  
Shihori Yokobayashi ◽  
Masayuki Yamamoto ◽  
Yoshinori Watanabe
Keyword(s):  
Fission Yeast ◽  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Specific Requirement ◽  
Spindle Poles ◽  
Chromatid Cohesion ◽  
Spindle Microtubules ◽  
Yeast Meiosis ◽  
Meiosis I ◽  
Random Division

ABSTRACT During mitosis, sister kinetochores attach to microtubules that extend to opposite spindle poles (bipolar attachment) and pull the chromatids apart at anaphase (equational segregation). A multisubunit complex called cohesin, including Rad21/Scc1, plays a crucial role in sister chromatid cohesion and equational segregation at mitosis. Meiosis I differs from mitosis in having a reductional pattern of chromosome segregation, in which sister kinetochores are attached to the same spindle (monopolar attachment). During meiosis, Rad21/Scc1 is largely replaced by its meiotic counterpart, Rec8. If Rec8 is inactivated in fission yeast, meiosis I is shifted from reductional to equational division. However, the reason rec8Δ cells undergo equational rather than random division has not been clarified; therefore, it has been unclear whether equational segregation is due to a loss of cohesin in general or to a loss of a specific requirement for Rec8. We report here that the equational segregation at meiosis I depends on substitutive Rad21, which relocates to the centromeres if Rec8 is absent. Moreover, we demonstrate that even if sufficient amounts of Rad21 are transferred to the centromeres at meiosis I, thereby establishing cohesion at the centromeres, rec8Δ cells never recover monopolar attachment but instead secure bipolar attachment. Thus, Rec8 and Rad21 define monopolar and bipolar attachment, respectively, at meiosis I. We conclude that cohesin is a crucial determinant of the attachment manner of kinetochores to the spindle microtubules at meiosis I in fission yeast.

Centromere Mapping Functions for Aneuploid Meiotic Products: Analysis of rec8, rec10 and rec11 Mutants of the Fission Yeast Schizosaccharomyces pombe

Genetics ◽  
1999 ◽  
Vol 153 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Michelle D Krawchuk ◽  
Wayne P Wahls
Keyword(s):  
Fission Yeast ◽  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Meiotic Division ◽  
Homologous Chromosomes ◽  
Mapping Functions ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Products Analysis ◽  
Meiosis I

AbstractRecent evidence suggests that the position of reciprocal recombination events (crossovers) is important for the segregation of homologous chromosomes during meiosis I and sister chromatids during meiosis II. We developed genetic mapping functions that permit the simultaneous analysis of centromere-proximal crossover recombination and the type of segregation error leading to aneuploidy. The mapping functions were tested in a study of the rec8, rec10, and rec11 mutants of fission yeast. In each mutant we monitored each of the three chromosome pairs. Between 38 and 100% of the chromosome segregation errors in the rec8 mutants were due to meiosis I nondisjunction of homologous chromosomes. The remaining segregation errors were likely the result of precocious separation of sister chromatids, a previously described defect in the rec8 mutants. Between 47 and 100% of segregation errors in the rec10 and rec11 mutants were due to nondisjunction of sister chromatids during meiosis II. In addition, centromere-proximal recombination was reduced as much as 14-fold or more on chromosomes that had experienced nondisjunction. These results demonstrate the utility of the new mapping functions and support models in which sister chromatid cohesion and crossover position are important determinants for proper chromosome segregation in each meiotic division.

scholarly journals Multiple Subunits of the Caenorhabditis elegans Anaphase-Promoting Complex Are Required for Chromosome Segregation During Meiosis I

Genetics ◽  
2002 ◽  
Vol 160 (2) ◽  
pp. 805-813 ◽  
Author(s):  
Edward S Davis ◽  
Lucia Wille ◽  
Barry A Chestnut ◽  
Penny L Sadler ◽  
Diane C Shakes ◽  
...  
Keyword(s):  
Rna Interference ◽  
Caenorhabditis Elegans ◽  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
Anaphase Promoting Complex ◽  
Genetic Screens ◽  
Chromatid Cohesion ◽  
Interference Studies ◽  
Meiosis I

Abstract Two genes, originally identified in genetic screens for Caenorhabditis elegans mutants that arrest in metaphase of meiosis I, prove to encode subunits of the anaphase-promoting complex or cyclosome (APC/C). RNA interference studies reveal that these and other APC/C subunits are essential for the segregation of chromosomal homologs during meiosis I. Further, chromosome segregation during meiosis I requires APC/C functions in addition to the release of sister chromatid cohesion.

scholarly journals Double or nothing: a Drosophila mutation affecting meiotic chromosome segregation in both females and males.

Genetics ◽  
1994 ◽  
Vol 136 (3) ◽  
pp. 953-964 ◽  
Author(s):  
D P Moore ◽  
W Y Miyazaki ◽  
J E Tomkiel ◽  
T L Orr-Weaver
Keyword(s):  
Cell Death ◽  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Meiotic Chromosome ◽  
Sister Chromatid Cohesion ◽  
Aberrant Chromosome ◽  
Chromatid Cohesion ◽  
Meiotic Nondisjunction ◽  
Lethal Allele ◽  
Meiosis I

Abstract We describe a Drosophila mutation, Double or nothing (Dub), that causes meiotic nondisjunction in a conditional, dominant manner. Previously isolated mutations in Drosophila specifically affect meiosis either in females or males, with the exception of the mei-S332 and ord genes which are required for proper sister-chromatid cohesion. Dub is unusual in that it causes aberrant chromosome segregation almost exclusively in meiosis I in both sexes. In Dub mutant females both nonexchange and exchange chromosomes undergo nondisjunction, but the effect of Dub on nonexchange chromosomes is more pronounced. Dub reduces recombination levels slightly. Multiple nondisjoined chromosomes frequently cosegregate to the same pole. Dub results in nondisjunction of all chromosomes in meiosis I of males, although the levels are lower than in females. When homozygous, Dub is a conditional lethal allele and exhibits phenotypes consistent with cell death.

scholarly journals ConnectingGCN5’s centromeric SAGA to the mitotic tension-sensing checkpoint

2018 ◽  
Vol 29 (18) ◽  
pp. 2201-2212 ◽  
Author(s):  
Emily L. Petty ◽  
Masha Evpak ◽  
Lorraine Pillus
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Spindle Assembly Checkpoint ◽  
Binding Function ◽  
Chromatid Cohesion ◽  
Histone H3 Variant ◽  
Spindle Microtubules ◽  
Low Tension ◽  
Centromere Histone H3 ◽  
Segregation Of Chromosomes

Multiple interdependent mechanisms ensure faithful segregation of chromosomes during cell division. Among these, the spindle assembly checkpoint monitors attachment of spindle microtubules to the centromere of each chromosome, whereas the tension-sensing checkpoint monitors the opposing forces between sister chromatid centromeres for proper biorientation. We report here a new function for the deeply conserved Gcn5 acetyltransferase in the centromeric localization of Rts1, a key player in the tension-sensing checkpoint. Rts1 is a regulatory component of protein phopshatase 2A, a near universal phosphatase complex, which is recruited to centromeres by the Shugoshin (Sgo) checkpoint component under low-tension conditions to maintain sister chromatid cohesion. We report that loss of Gcn5 disrupts centromeric localization of Rts1. Increased RTS1 dosage robustly suppresses gcn5∆ cell cycle and chromosome segregation defects, including restoration of Rts1 to centromeres. Sgo1’s Rts1-binding function also plays a key role in RTS1 dosage suppression of gcn5∆ phenotypes. Notably, we have identified residues of the centromere histone H3 variant Cse4 that function in these chromosome segregation-related roles of RTS1. Together, these findings expand the understanding of the mechanistic roles of Gcn5 and Cse4 in chromosome segregation.

scholarly journals Spindle checkpoint activation at meiosis I advances anaphase II onset via meiosis-specific APC/C regulation

2008 ◽  
Vol 182 (2) ◽  
pp. 277-288 ◽  
Author(s):  
Ayumu Yamamoto ◽  
Kenji Kitamura ◽  
Daisuke Hihara ◽  
Yukinobu Hirose ◽  
Satoshi Katsuyama ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Fission Yeast ◽  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Related Factor ◽  
Anaphase Promoting Complex ◽  
Checkpoint Activation ◽  
Anaphase Onset ◽  
Yeast Meiosis ◽  
Meiosis I

During mitosis, the spindle assembly checkpoint (SAC) inhibits the Cdc20-activated anaphase-promoting complex/cyclosome (APC/CCdc20), which promotes protein degradation, and delays anaphase onset to ensure accurate chromosome segregation. However, the SAC function in meiotic anaphase regulation is poorly understood. Here, we examined the SAC function in fission yeast meiosis. As in mitosis, a SAC factor, Mad2, delayed anaphase onset via Slp1 (fission yeast Cdc20) when chromosomes attach to the spindle improperly. However, when the SAC delayed anaphase I, the interval between meiosis I and II shortened. Furthermore, anaphase onset was advanced and the SAC effect was reduced at meiosis II. The advancement of anaphase onset depended on a meiosis-specific, Cdc20-related factor, Fzr1/Mfr1, which contributed to anaphase cyclin decline and anaphase onset and was inefficiently inhibited by the SAC. Our findings show that impacts of SAC activation are not confined to a single division at meiosis due to meiosis-specific APC/C regulation, which has probably been evolved for execution of two meiotic divisions.

scholarly journals Rec8p, a Meiotic Recombination and Sister Chromatid Cohesion Phosphoprotein of the Rad21p Family Conserved from Fission Yeast to Humans

1999 ◽  
Vol 19 (5) ◽  
pp. 3515-3528 ◽  
Author(s):  
Sandro Parisi ◽  
Michael J. McKay ◽  
Monika Molnar ◽  
M. Anne Thompson ◽  
Peter J. van der Spek ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Sister Chromatid ◽  
Germ Line ◽  
Sequence Similarity ◽  
Sister Chromatid Cohesion ◽  
Specific Expression ◽  
Chromatid Cohesion ◽  
Prophase Nucleus ◽  
Chromosome Iii ◽  
Meiosis I

ABSTRACT Our work and that of others defined mitosis-specific (Rad21 subfamily) and meiosis-specific (Rec8 subfamily) proteins involved in sister chromatid cohesion in several eukaryotes, including humans. Mutation of the fission yeast Schizosaccharomyces pombe rec8 gene was previously shown to confer a number of meiotic phenotypes, including strong reduction of recombination frequencies in the central region of chromosome III, absence of linear element polymerization, reduced pairing of homologous chromosomes, reduced sister chromatid cohesion, aberrant chromosome segregation, defects in spore formation, and reduced spore viability. Here we extend the description of recombination reduction to the central regions of chromosomes I and II. We show at the protein level that expression ofrec8 is meiosis specific and that Rec8p localizes to approximately 100 foci per prophase nucleus. Rec8p was present in an unphosphorylated form early in meiotic prophase but was phosphorylated prior to meiosis I, as demonstrated by analysis of the mei4mutant blocked before meiosis I. Evidence for the persistence of Rec8p beyond meiosis I was obtained by analysis of the mutantmes1 blocked before meiosis II. A human gene, which we designate hrec8, showed significant primary sequence similarity to rec8 and was mapped to chromosome 14. High mRNA expression of mouse and human rec8 genes was found only in germ line cells, specifically in testes and, interestingly, in spermatids. hrec8 was also expressed at a low level in the thymus. Sequence similarity and testis-specific expression indicate evolutionarily conserved functions of Rec8p in meiosis. Possible roles of Rec8p in the integration of different meiotic events are discussed.

scholarly journals Human kinetochores are swivel joints that mediate microtubule attachments

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Chris A Smith ◽  
Andrew D McAinsh ◽  
Nigel J Burroughs
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Mitotic Spindle ◽  
Three Dimensional ◽  
Organisational Change ◽  
Mechanical Process ◽  
Spindle Poles ◽  
Chromatid Cohesion ◽  
Sister Kinetochore ◽  
Dynamic Microtubule

Chromosome segregation is a mechanical process that requires assembly of the mitotic spindle – a dynamic microtubule-based force-generating machine. Connections to this spindle are mediated by sister kinetochore pairs, that form dynamic end-on attachments to microtubules emanating from opposite spindle poles. This bi-orientation generates forces that have been reported to stretch the kinetochore itself, which has been suggested to stabilise attachment and silence the spindle checkpoint. We reveal using three dimensional tracking that the outer kinetochore domain can swivel around the inner kinetochore/centromere, which results in large reductions in intra-kinetochore distance (delta) when viewed in lower dimensions. We show that swivel provides a mechanical flexibility that enables kinetochores at the periphery of the spindle to engage microtubules. Swivel reduces as cells approach anaphase, suggesting an organisational change linked to checkpoint satisfaction and/or obligatory changes in kinetochore mechanochemistry may occur before dissolution of sister chromatid cohesion.

Live observation of fission yeast meiosis in recombination-deficient mutants

2001 ◽  
Vol 114 (15) ◽  
pp. 2843-2853 ◽  
Author(s):  
Monika Molnar ◽  
Jürg Bähler ◽  
Jürg Kohli ◽  
Yasushi Hiraoka
Keyword(s):  
Fission Yeast ◽  
Chromosome Segregation ◽  
Meiotic Division ◽  
Chiasma Formation ◽  
Homologous Chromosomes ◽  
Yeast Meiosis ◽  
Mutant Cells ◽  
Random Level ◽  
Meiosis I ◽  
Chromosome Disjunction

Regular segregation of homologous chromosomes during meiotic divisions is essential for the generation of viable progeny. In recombination-proficient organisms, chromosome disjunction at meiosis I generally occurs by chiasma formation between the homologs (chiasmate meiosis). We have studied meiotic stages in living rec8 and rec7 mutant cells of fission yeast, with special attention to prophase and the first meiotic division. Both rec8 and rec7 are early recombination mutants, and in rec7 mutants, chromosome segregation at meiosis I occurs without any recombination (achiasmate meiosis). Both mutants showed distinct irregularities in nuclear prophase movements. Additionally, rec7 showed an extended first division of variable length and with single chromosomes changing back and forth between the cell poles. Two other early recombination deficient mutants (rec14 and rec15) showed very similar phenotypes to rec7 during the first meiotic division, and the fidelity of achiasmate chromosome segregation slightly exceeded the expected random level. We discuss possible regulatory mechanisms of fission yeast to deal with achiasmate chromosome segregation.

scholarly journals Mitotic Chromosome Biorientation in Fission Yeast Is Enhanced by Dynein and a Minus-end–directed, Kinesin-like Protein

2007 ◽  
Vol 18 (6) ◽  
pp. 2216-2225 ◽  
Author(s):  
Ekaterina L. Grishchuk ◽  
Ilia S. Spiridonov ◽  
J. Richard McIntosh
Keyword(s):  
Fission Yeast ◽  
Chromosome Segregation ◽  
Mitotic Chromosome ◽  
Spindle Pole ◽  
Ultrastructural Analysis ◽  
Yeast Cells ◽  
Mitotic Spindles ◽  
Wild Type ◽  
Spindle Poles ◽  
Spindle Microtubules

Chromosome biorientation, the attachment of sister kinetochores to sister spindle poles, is vitally important for accurate chromosome segregation. We have studied this process by following the congression of pole-proximal kinetochores and their subsequent anaphase segregation in fission yeast cells that carry deletions in any or all of this organism's minus end–directed, microtubule-dependent motors: two related kinesin 14s (Pkl1p and Klp2p) and dynein. None of these deletions abolished biorientation, but fewer chromosomes segregated normally without Pkl1p, and to a lesser degree without dynein, than in wild-type cells. In the absence of Pkl1p, which normally localizes to the spindle and its poles, the checkpoint that monitors chromosome biorientation was defective, leading to frequent precocious anaphase. Ultrastructural analysis of mutant mitotic spindles suggests that Pkl1p contributes to error-free biorientation by promoting normal spindle pole organization, whereas dynein helps to anchor a focused bundle of spindle microtubules at the pole.

scholarly journals Spindle checkpoint–independent inhibition of mitotic chromosome segregation byDrosophilaMps1

2012 ◽  
Vol 23 (12) ◽  
pp. 2275-2291 ◽  
Author(s):  
Friederike Althoff ◽  
Roger E. Karess ◽  
Christian F. Lehner
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Spindle Assembly Checkpoint ◽  
Mitotic Chromosome ◽  
Independent Manner ◽  
Spindle Poles ◽  
Anaphase Onset ◽  
Chromosome Congression ◽  
Monopolar Spindle ◽  
Chromatid Cohesion

Monopolar spindle 1 (Mps1) is essential for the spindle assembly checkpoint (SAC), which prevents anaphase onset in the presence of misaligned chromosomes. Moreover, Mps1 kinase contributes in a SAC-independent manner to the correction of erroneous initial attachments of chromosomes to the spindle. Our characterization of the Drosophila homologue reveals yet another SAC-independent role. As in yeast, modest overexpression of Drosophila Mps1 is sufficient to delay progression through mitosis during metaphase, even though chromosome congression and metaphase alignment do not appear to be affected. This delay in metaphase depends on the SAC component Mad2. Although Mps1 overexpression in mad2 mutants no longer causes a metaphase delay, it perturbs anaphase. Sister kinetochores barely move apart toward spindle poles. However, kinetochore movements can be restored experimentally by separase-independent resolution of sister chromatid cohesion. We propose therefore that Mps1 inhibits sister chromatid separation in a SAC-independent manner. Moreover, we report unexpected results concerning the requirement of Mps1 dimerization and kinase activity for its kinetochore localization in Drosophila. These findings further expand Mps1's significance for faithful mitotic chromosome segregation and emphasize the importance of its careful regulation.

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