Fission yeast Pds5 is required for accurate chromosome segregation and for survival after DNA damage or metaphase arrest

2002 ◽  
Vol 115 (3) ◽  
pp. 587-598 ◽  
Author(s):  
Shao-Win Wang ◽  
Rebecca L. Read ◽  
Chris J. Norbury
Keyword(s):  
Dna Damage ◽  
Fission Yeast ◽  
Sister Chromatid ◽  
Budding Yeast ◽  
Eukaryotic Cell ◽  
Sister Chromatid Cohesion ◽  
Chromosome Loss ◽  
Dependent Manner ◽  
Yeast Saccharomyces Cerevisiae ◽  
Chromatid Cohesion

Sister chromatid cohesion, which is established during the S phase of the eukaryotic cell cycle and persists until the onset of anaphase, is essential for the maintenance of genomic integrity. Cohesion requires the multi-protein complex cohesin, as well as a number of accessory proteins including Pds5/BIMD/Spo76. In the budding yeast Saccharomyces cerevisiae Pds5 is an essential protein that localises to chromosomes in a cohesin-dependent manner. Here we describe the characterisation in the fission yeast Schizosaccharomyces pombe of pds5+, a novel,non-essential orthologue of S. cerevisiae PDS5. The S. pombePds5 protein was localised to punctate nuclear foci in a manner that was dependent on the Rad21 cohesin component. This, together with additional genetic evidence, points towards an involvement of S. pombe Pds5 in sister chromatid cohesion. S. pombe pds5 mutants were hypersensitive to DNA damage and to mitotic metaphase delay, but this sensitivity was apparently not due to precocious loss of sister chromatid cohesion. These cells also suffered increased spontaneous chromosome loss and meiotic defects and their viability was dependent on the spindle checkpoint protein Bub1. Thus, while S. pombe Pds5 has an important cohesin-related role, this differs significantly from that of the equivalent budding yeast protein.

scholarly journals Mutational Analysis of the Drosophila Sister-Chromatid Cohesion Protein ORD and Its Role in the Maintenance of Centromeric Cohesion

Genetics ◽  
1997 ◽  
Vol 146 (4) ◽  
pp. 1319-1331 ◽  
Author(s):  
Sharon E Bickel ◽  
Dudley W Wyman ◽  
Terry L Orr-Weaver
Keyword(s):  
Sister Chromatid ◽  
Mutational Analysis ◽  
Germ Line ◽  
Sister Chromatid Cohesion ◽  
Chromosome Loss ◽  
Male And Female ◽  
Chromatid Cohesion ◽  
Random Segregation ◽  
Kinetochore Function ◽  
Segregation Of Chromosomes

The ord gene is required for proper segregation of all chromosomes in both male and female Drosophila meiosis. Here we describe the isolation of a null ord allele and examine the consequences of ablating ord function. Cytologically, meiotic sister-chromatid cohesion is severely disrupted in flies lacking ORD protein. Moreover, the frequency of missegregation in genetic tests is consistent with random segregation of chromosomes through both meiotic divisions, suggesting that sister cohesion may be completely abolished. However, only a slight decrease in viability is observed for ord null flies, indicating that ORD function is not essential for cohesion during somatic mitosis. In addition, we do not observe perturbation of germ-line mitotic divisions in flies lacking ORD activity. Our analysis of weaker ord alleles suggests that ORD is required for proper centromeric cohesion after arm cohesion is released at the metaphase I/anaphase I transition. Finally, although meiotic cohesion is abolished in the ord null fly, chromosome loss is not appreciable. Therefore, ORD activity appears to promote centromeric cohesion during meiosis II but is not essential for kinetochore function during anaphase.

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 Reduced Mad2 expression keeps relaxed kinetochores from arresting budding yeast in mitosis

2011 ◽  
Vol 22 (14) ◽  
pp. 2448-2457 ◽  
Author(s):  
Erin L. Barnhart ◽  
Russell K. Dorer ◽  
Andrew W. Murray ◽  
Scott C. Schuyler
Keyword(s):  
Chromosome Segregation ◽  
Budding Yeast ◽  
Spindle Checkpoint ◽  
Chromosome Loss ◽  
Wild Type ◽  
Yeast Saccharomyces Cerevisiae ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Diploid Cells ◽  
Antimicrotubule Drugs

Chromosome segregation depends on the spindle checkpoint, which delays anaphase until all chromosomes have bound microtubules and have been placed under tension. The Mad1–Mad2 complex is an essential component of the checkpoint. We studied the consequences of removing one copy of MAD2 in diploid cells of the budding yeast, Saccharomyces cerevisiae. Compared to MAD2/MAD2 cells, MAD2/mad2Δ heterozygotes show increased chromosome loss and have different responses to two insults that activate the spindle checkpoint: MAD2/mad2Δ cells respond normally to antimicrotubule drugs but cannot respond to chromosomes that lack tension between sister chromatids. In MAD2/mad2Δ cells with normal sister chromatid cohesion, removing one copy of MAD1 restores the checkpoint and returns chromosome loss to wild-type levels. We conclude that cells need the normal Mad2:Mad1 ratio to respond to chromosomes that are not under tension.

scholarly journals Hsp90 Is Essential for Chl1-Mediated Chromosome Segregation and Sister Chromatid Cohesion

mSphere ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Nidhi Khurana ◽  
Sayan Bakshi ◽  
Wahida Tabassum ◽  
Mrinal K. Bhattacharyya ◽  
Sunanda Bhattacharyya
Keyword(s):  
Sister Chromatid ◽  
Hsp90 Inhibitor ◽  
Sister Chromatid Cohesion ◽  
Chromosome Loss ◽  
Temperature Sensitive ◽  
Restrictive Temperature ◽  
Functional Loss ◽  
Mechanistic Insight ◽  
Chromatid Cohesion ◽  
Insight Into

ABSTRACT Recent studies have demonstrated that aberrant sister chromatid cohesion causes genomic instability and hence is responsible for the development of a tumor. The Chl1 (chromosome loss 1) protein (homolog of human ChlRl/DDX11 helicase) plays an essential role in the proper segregation of chromosomes during mitosis. The helicase activity of Chl1 is critical for sister chromatid cohesion. Our study demonstrates that Hsp90 interacts with Chl1 and is necessary for its stability. We observe that the Hsp90 nonfunctional condition (temperature-sensitive iG170Dhsp82 strain at restrictive temperature) induces proteasomal degradation of Chl1. We have mapped the domains of Chl1 and identified that the presence of domains II, III, and IV is essential for efficient interaction with Hsp90. We have demonstrated that Hsp90 inhibitor 17-AAG (17-allylamino-geldenamycin) causes destabilization of Chl1 protein and enhances significant disruption of sister chromatid cohesion, which is comparable to that observed under the Δchl1 condition. Our study also revealed that 17-AAG treatment causes an increased frequency of chromosome loss to a similar extent as that of the Δchl1 cells. Hsp90 functional loss has been earlier linked to aneuploidy with very poor mechanistic insight. Our result identifies Chl1 as a novel client of Hsp90, which could be further explored to gain mechanistic insight into aneuploidy. IMPORTANCE Recently, Hsp90 functional loss has been linked to aneuploidy; however, until now none of the components of sister chromatid cohesion (SCC) have been demonstrated as the putative clients of Hsp90. In this study, we have established that Chl1, the protein which is involved in maintaining sister chromatid cohesion as well as in preventing chromosome loss, is a direct client of Hsp90. Thus, with understanding of the molecular mechanism, how Hsp90 controls the cohesion machinery might reveal new insights which can be exploited further for attenuation of tumorigenesis.

scholarly journals Pericentromeric Sister Chromatid Cohesion Promotes Kinetochore Biorientation

2009 ◽  
Vol 20 (17) ◽  
pp. 3818-3827 ◽  
Author(s):  
Tessie M. Ng ◽  
William G. Waples ◽  
Brigitte D. Lavoie ◽  
Sue Biggins
Keyword(s):  
Protein Kinase ◽  
Genetic Analysis ◽  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Budding Yeast ◽  
Sister Chromatid Cohesion ◽  
Specific Role ◽  
Aurora B ◽  
Chromatid Cohesion ◽  
Yeast Genes

Accurate chromosome segregation depends on sister kinetochores making bioriented attachments to microtubules from opposite poles. An essential regulator of biorientation is the Ipl1/Aurora B protein kinase that destabilizes improper microtubule–kinetochore attachments. To identify additional biorientation pathways, we performed a systematic genetic analysis between the ipl1-321 allele and all nonessential budding yeast genes. One of the mutants, mcm21Δ, precociously separates pericentromeres and this is associated with a defect in the binding of the Scc2 cohesin-loading factor at the centromere. Strikingly, Mcm21 becomes essential for biorientation when Ipl1 function is reduced, and this appears to be related to its role in pericentromeric cohesion. When pericentromeres are artificially tethered, Mcm21 is no longer needed for biorientation despite decreased Ipl1 activity. Taken together, these data reveal a specific role for pericentromeric linkage in ensuring kinetochore biorientation.

scholarly journals Budding yeast PDS5 plays an important role in meiosis and is required for sister chromatid cohesion

2005 ◽  
Vol 56 (3) ◽  
pp. 670-680 ◽  
Author(s):  
Zhaojie Zhang ◽  
Qun Ren ◽  
Hui Yang ◽  
Michael N. Conrad ◽  
Vincent Guacci ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Budding Yeast ◽  
Sister Chromatid Cohesion ◽  
Chromatid Cohesion
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