A Cohesin-Based Partitioning Mechanism Revealed upon Transcriptional Inactivation of Centromere

Autor: Kerry Bloom, Julian Haase, Brittany N. Eldridge, Michael Tsabar, Rebecca M. Hine, James E. Haber, Lila Kaminsky, Chloe E. Snider, Benjamin D. Harrison
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Cancer Research
Chromosomal Proteins
Non-Histone
Cell Cycle Proteins
Haploidy
Chromosome segregation
Chromosomal Disorders
Chromosome Segregation
Medicine and Health Sciences
Cell Cycle and Cell Division
Kinetochores
Genetics (clinical)
Anaphase
Genetics
Centromeres
Kinetochore
Chromosome Biology
Organic Compounds
Monosaccharides
DNA-Binding Proteins
Chemistry
Cell Processes
Physical Sciences
Chromatid
Research Article
Transcriptional Activation
congenital
hereditary
and neonatal diseases and abnormalities
Chromosome Structure and Function
Saccharomyces cerevisiae Proteins
lcsh:QH426-470
Cell Survival
Kinetochore assembly
Centromere
Carbohydrates
Saccharomyces cerevisiae
Spindle Apparatus
Biology
Chromosomes
03 medical and health sciences
Molecular Biology
Ecology
Evolution
Behavior and Systematics
Metaphase
Clinical Genetics
Cohesin
Organic Chemistry
Chemical Compounds
Biology and Life Sciences
Galactose
Cell Biology
Spindle apparatus
lcsh:Genetics
030104 developmental biology
Glucose
Zdroj: PLoS Genetics
PLoS Genetics, Vol 12, Iss 4, p e1006021 (2016)
ISSN: 1553-7404
1553-7390
Popis: Transcriptional inactivation of the budding yeast centromere has been a widely used tool in studies of chromosome segregation and aneuploidy. In haploid cells when an essential chromosome contains a single conditionally inactivated centromere (GAL-CEN), cell growth rate is slowed and segregation fidelity is reduced; but colony formation is nearly 100%. Pedigree analysis revealed that only 30% of the time both mother and daughter cell inherit the GAL-CEN chromosome. The reduced segregation capacity of the GAL-CEN chromosome is further compromised upon reduction of pericentric cohesin (mcm21∆), as reflected in a further diminishment of the Mif2 kinetochore protein at GAL-CEN. By redistributing cohesin from the nucleolus to the pericentromere (by deleting SIR2), there is increased presence of the kinetochore protein Mif2 at GAL-CEN and restoration of cell viability. These studies identify the ability of cohesin to promote chromosome segregation via kinetochore assembly, in a situation where the centromere has been severely compromised.
Author Summary Studies of kinetochore organization and function led to the development of conditionally inactivated centromeres. The most commonly used conditionally inactivated centromere tool is the insertion of a galactose inducible promoter upstream of the centromeric sequence, termed GAL-CEN. Viability of haploid cells containing GAL-CEN3 grown on galactose is close to 100%, despite having an inactivated centromere. Inactivation of CEN3 leads to aberrant segregation of sister chromatids in metaphase, and an impairment in recruitment of centromeric proteins. Strikingly, when pericentromeric cohesin recruitment is impaired by deleting MCM21, viability is reduced to 23%. Moreover, mcm21Δ GAL-CEN3 cells demonstrate a more pronounced sister chromatid segregation defect and reduced recruitment of the kinetochore protein Mif2 as compared to GAL-CEN3 alone. The defects observed in mcm21Δ are rescued to GAL-CEN3 WT levels by deletion of SIR2, which restores cohesin recruitment to the pericentromeric regions in mcm21Δ. Our data suggests cohesin plays a role in centromere function to serve as a template for proper kinetochore structure.
Databáze: OpenAIRE
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