Protein kinases in mitotic phosphorylation of budding yeast CENP-A

Mishra, Prashant; Basrai, Munira A.

doi:10.1007/s00294-019-00997-5

Cited by 8 publications

(16 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Second, Cdc5 has been shown to interact with both Cse4 and Ndc80 [25] and phosphorylate microtubule-associated proteins (MAPs) such as Stu2 and Slk19 [40] and the SAC component Mad3 [41]. Third, phosphorylation of Cse4 by both Cdc5 and Ipl1 Aurora B kinase is important for faithful chromosome segregation [42]. Fourth, Cdc5 responds to CDK phosphorylation, making it a good candidate for facilitating or amplifying cell cycle signals at the kinetochore.…”

Section: Constitutive Cdc5 Kinase Activity At Different Kinetochore Smentioning

confidence: 99%

Polo kinase recruitment via the constitutive centromere-associated network at the kinetochore elevates centromeric RNA

Ólafsson

Thorpe

2020

PLoS Genet

View full text Add to dashboard Cite

The kinetochore, a multi-protein complex assembled on centromeres, is essential to segregate chromosomes during cell division. Deficiencies in kinetochore function can lead to chromosomal instability and aneuploidy-a hallmark of cancer cells. Kinetochore function is controlled by recruitment of regulatory proteins, many of which have been documented, however their function often remains uncharacterized and many are yet to be identified. To identify candidates of kinetochore regulation we used a proteome-wide protein association strategy in budding yeast and detected many proteins that are involved in post-translational modifications such as kinases, phosphatases and histone modifiers. We focused on the Polo-like kinase, Cdc5, and interrogated which cellular components were sensitive to constitutive Cdc5 localization. The kinetochore is particularly sensitive to constitutive Cdc5 kinase activity. Targeting Cdc5 to different kinetochore subcomplexes produced diverse phenotypes, consistent with multiple distinct functions at the kinetochore. We show that targeting Cdc5 to the inner kinetochore, the constitutive centromere-associated network (CCAN), increases the levels of centromeric RNA via an SPT4 dependent mechanism.

show abstract

Section: Constitutive Cdc5 Kinase Activity At Different Kinetochore Smentioning

confidence: 99%

Polo kinase recruitment via the constitutive centromere-associated network at the kinetochore elevates centromeric RNA

Ólafsson

Thorpe

2020

PLoS Genet

View full text Add to dashboard Cite

show abstract

“…Moreover, active Cdc5 facilitates sister chromatid separation. Recent advances about the role of Cdc5 kinase in faithful chromosome segregation are reviewed by Mishra and Basrai [50].…”

Section: Cdc5 Kinasementioning

confidence: 99%

The Opposing Functions of Protein Kinases and Phosphatases in Chromosome Bipolar Attachment

Sherwin

Wang

2019

IJMS

View full text Add to dashboard Cite

Accurate chromosome segregation during cell division is essential to maintain genome integrity in all eukaryotic cells, and chromosome missegregation leads to aneuploidy and therefore represents a hallmark of many cancers. Accurate segregation requires sister kinetochores to attach to microtubules emanating from opposite spindle poles, known as bipolar attachment or biorientation. Recent studies have uncovered several mechanisms critical to chromosome bipolar attachment. First, a mechanism exists to ensure that the conformation of sister centromeres is biased toward bipolar attachment. Second, the phosphorylation of some kinetochore proteins destabilizes kinetochore attachment to facilitate error correction, but a protein phosphatase reverses this phosphorylation. Moreover, the activity of the spindle assembly checkpoint is regulated by kinases and phosphatases at the kinetochore, and this checkpoint prevents anaphase entry in response to faulty kinetochore attachment. The fine-tuned kinase/phosphatase balance at kinetochores is crucial for faithful chromosome segregation during both mitosis and meiosis. Here, we discuss the function and regulation of protein phosphatases in the establishment of chromosome bipolar attachment with a focus on the model organism budding yeast.

show abstract

“…We previously identified two kinases, Ipl1 (Aurora B kinase in humans) and Cdc5 (Plk1 in humans), that phosphorylate Cse4 to prevent CIN ( Boeckmann et al. , 2013 ; Mishra and Basrai, 2019 ; Mishra et al. , 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…Ipl1‑mediated phosphorylation of Cse4 regulates kinetochore–microtubule interactions and chromosome biorientation ( Boeckmann et al. , 2013 ; Mishra and Basrai, 2019 ), whereas Cdc5‑mediated mitotic phosphorylation of Cse4 contributes to high-fidelity chromosome segregation ( Mishra and Basrai, 2019 ; Mishra et al. , 2019 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cdc7-mediated phosphorylation of Cse4 regulates high-fidelity chromosome segregation in budding yeast

Mishra

Wood

Stanton

et al. 2021

MBoC

Self Cite

View full text Add to dashboard Cite

Faithful chromosome segregation maintains chromosomal stability as errors in this process contribute to chromosomal instability (CIN) which has been observed in many diseases including cancer. Epigenetic regulation of kinetochore proteins such as Cse4 (CENP-A in humans) plays a critical role in high fidelity chromosome segregation. Here we show that Cse4 is a substrate of evolutionarily conserved Cdc7 kinase, and that Cdc7-mediated phosphorylation of Cse4 prevents CIN. We determined that Cdc7 phosphorylates Cse4 in vitro and interacts with Cse4 in vivo in a cell cycle dependent manner. Cdc7 is required for kinetochore integrity as reduced levels of CEN-associated Cse4, a faster exchange of Cse4 at the metaphase kinetochores and defects in chromosome segregation are observed in a cdc7-7 strain. Phosphorylation of Cse4 by Cdc7 is important for cell survival as constitutive association of a kinase dead variant of Cdc7 ( cdc7-kd) with Cse4 at the kinetochore leads to growth defects. Moreover, phosphodeficient mutations of Cse4 for consensus Cdc7 target sites contribute to CIN phenotype. In summary, our results have defined a role for Cdc7-mediated phosphorylation of Cse4 in faithful chromosome segregation.

show abstract

Protein kinases in mitotic phosphorylation of budding yeast CENP-A

Cited by 8 publications

References 73 publications

Polo kinase recruitment via the constitutive centromere-associated network at the kinetochore elevates centromeric RNA

Polo kinase recruitment via the constitutive centromere-associated network at the kinetochore elevates centromeric RNA

The Opposing Functions of Protein Kinases and Phosphatases in Chromosome Bipolar Attachment

Cdc7-mediated phosphorylation of Cse4 regulates high-fidelity chromosome segregation in budding yeast

Contact Info

Product

Resources

About