Cep57 and Cep57L1 maintain centriole engagement in interphase to ensure centriole duplication cycle

Centrioles duplicate in interphase only once per cell cycle. Newly formed centrioles remain associated with their mother centrioles. The two centrioles disengage at the end of mitosis, which licenses centriole duplication in the next cell cycle. Therefore, timely centriole disengagement is critical for the proper centriole duplication cycle. However, the mechanisms underlying centriole engagement during interphase are poorly understood. Here, we show that Cep57 and Cep57L1 cooperatively maintain centriole engagement during interphase. Codepletion of Cep57 and Cep57L1 induces precocious centriole disengagement in interphase without compromising cell cycle progression. The disengaged daughter centrioles convert into centrosomes during interphase in a Plk1-dependent manner. Furthermore, the centrioles reduplicate and the centriole number increases, which results in chromosome segregation errors. Overall, these findings demonstrate that the maintenance of centriole engagement by Cep57 and Cep57L1 during interphase is crucial for the tight control of centriole copy number and thus for proper chromosome segregation.

Growth disadvantage associated with centrosome amplification drives population-level centriole number homeostasis

The centriole duplication cycle normally maintains number at two centrioles per G1 cell. However, some circumstances can result in an aberrant increase in centriole number. Cells with extra centrioles display extended cell cycle arrest, longer interphase durations, and death, which result in a proliferative disadvantage relative to normal cells.

Orderly assembly underpinning built-in asymmetry in the yeast centrosome duplication cycle requires cyclin-dependent kinase

Asymmetric astral microtubule organization drives the polarized orientation of the S. cerevisiae mitotic spindle and primes the invariant inheritance of the old spindle pole body (SPB, the yeast centrosome) by the bud. This model has anticipated analogous centrosome asymmetries featured in self-renewing stem cell divisions. We previously implicated Spc72, the cytoplasmic receptor for the gamma-tubulin nucleation complex, as the most upstream determinant linking SPB age, functional asymmetry and fate. Here we used structured illumination microscopy and biochemical analysis to explore the asymmetric landscape of nucleation sites inherently built into the spindle pathway and under the control of cyclin-dependent kinase (CDK). We show that CDK enforces Spc72 asymmetric docking by phosphorylating Nud1/centriolin. Furthermore, CDK-imposed order in the construction of the new SPB promotes the correct balance of nucleation sites between the nuclear and cytoplasmic faces of the SPB. Together these contributions by CDK inherently link correct SPB morphogenesis, age and fate.

Orderly assembly underpinning built-in asymmetry in the yeast centrosome duplication cycle requires cyclin-dependent kinase

ABSTRACTAsymmetric astral microtubule organization drives the polarized orientation of the S. cerevisiae mitotic spindle and primes the invariant inheritance of the old spindle pole body (SPB, the yeast centrosome) by the bud. This model has anticipated analogous centrosome asymmetries featuring in self-renewing stem cell divisions. We previously implicated Spc72, the cytoplasmic receptor for the gamma-tubulin nucleation complex, as the most upstream determinant linking SPB age, functional asymmetry and fate. Here we used structured illumination microscopy and biochemical analysis to explore the asymmetric landscape of nucleation sites inherently built into the spindle pathway and under the control of cyclin-dependent kinase (CDK). We show that CDK enforces Spc72 asymmetric docking by phosphorylating Nud1/centriolin. Furthermore, CDK-imposed order in the construction of the new SPB promotes the correct balance of nucleation sites between the nuclear and cytoplasmic faces of the SPB. Together these contributions by CDK inherently link correct SPB morphogenesis, age and fate.

DONSON, a gene responsible for microcephalic primordial dwarfism, ensures proper centriole duplication cycle by maintaining centriole engagement during interphase

Microcephalic primordial dwarfism (MPD) is a genetic disorder characterized by short stature and microcephaly. MPD-related genes are known to regulate centrosome biogenesis, DNA replication or the DNA damage response. Although some of the MPD-related proteins that are implicated in DNA replication localize to centrosomes, how these proteins affect centrosome biogenesis remains mostly elusive. Here, we revisit the potential function of these DNA replication mediators in human centrosome biogenesis. Among these proteins, depletion of DONSON leads to excessive number of centrosomes in interphase, caused by precocious centriole disengagement. Such disengaged centrioles are converted to centrosomes, followed by centriole reduplication during interphase. These extra centrosomes lead to abnormal spindle formation and chromosome segregation errors. Importantly, similar defects are observed in MPD patients’ cells with DONSON mutations, suggesting a possible cause of the disease. Overall, these results indicate that DONSON is involved in regulating the centriole duplication cycle by ensuring the maintenance of centriole engagement during interphase.

Cep57 and Cep57L1 cooperatively maintain centriole engagement during interphase to ensure proper centriole duplication cycle

Centrioles duplicate in the interphase only once per cell cycle. Newly formed centrioles remain associated with their mother centrioles. The two centrioles disengage at the end of mitosis, which licenses centriole duplication in the next cell cycle. Therefore, timely centriole disengagement is critical for the proper centriole duplication cycle. However, the mechanisms underlying centriole engagement during interphase are poorly understood. Here, we show that Cep57 and Cep57L1 cooperatively maintain centriole engagement during interphase. Co-depletion of Cep57 and Cep57L1 induces precocious centriole disengagement in the interphase without compromising cell cycle progression. The disengaged daughter centrioles convert into centrosomes during interphase in a Plk1-dependent manner. Furthermore, the centrioles reduplicate and the centriole number increases, which results in chromosome segregation errors. Overall, these findings demonstrate that the maintenance of centriole engagement by Cep57 and Cep57L1 during interphase is crucial for the tight control of centriole copy number and thus for proper chromosome segregation.

Cytokinesis in Eukaryotic Cells: The Furrow Complexity at a Glance

The duplication cycle is the fascinating process that, starting from a cell, results in the formation of two daughter cells and it is essential for life. Cytokinesis is the final step of the cell cycle, it is a very complex phase, and is a concert of forces, remodeling, trafficking, and cell signaling. All of the steps of cell division must be properly coordinated with each other to faithfully segregate the genetic material and this task is fundamental for generating viable cells. Given the importance of this process, molecular pathways and proteins that are involved in cytokinesis are conserved from yeast to humans. In this review, we describe symmetric and asymmetric cell division in animal cell and in a model organism, budding yeast. In addition, we illustrate the surveillance mechanisms that ensure a proper cell division and discuss the connections with normal cell proliferation and organs development and with the occurrence of human diseases.

Fast and furious . . . or not, Plk4 dictates the pace

In each duplication cycle, daughter centrioles grow to the same length as their mothers. Which mechanisms regulate this fidelity to maintain centriole length is not known. In this issue, Aydogan et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201801014) report a novel role for Polo-like kinase 4 (Plk4). They found that Plk4 functions in a homeostatic manner to balance growth rate and growth period to set the final centriole size.