scholarly journals G2/M Arrest Caused by Actin Disruption Is a Manifestation of the Cell Size Checkpoint in Fission Yeast

2001 ◽  
Vol 12 (12) ◽  
pp. 3892-3903 ◽  
Author(s):  
Ivan Rupes̆ ◽  
Bradley A. Webb ◽  
Alan Mak ◽  
Paul G. Young
Keyword(s):  
Cell Size ◽  
Budding Yeast ◽  
Tyrosine Phosphatase ◽  
Careful Analysis ◽  
Cell Cycle Checkpoint ◽  
Size Monitoring ◽  
Inhibitory Tyrosine Phosphorylation ◽  
Cycle Checkpoint ◽  
Size Threshold ◽  
Cdc25 Protein

In budding yeast, actin disruption prevents nuclear division. This has been explained as activation of a morphogenesis checkpoint monitoring the integrity of the actin cytoskeleton. The checkpoint operates through inhibitory tyrosine phosphorylation of Cdc28, the budding yeast Cdc2 homolog. Wild-type Schizosaccharomyces pombe cells also arrest before mitosis after actin depolymerization. Oversized cells, however, enter mitosis uninhibited. We carried out a careful analysis of the kinetics of mitotic initiation after actin disruption in undersized and oversized cells. We show that an inability to reach the mitotic size threshold explains the arrest in smaller cells. Among the regulators that control the level of the inhibitory Cdc2-Tyr15 phosphorylation, the Cdc25 protein tyrosine phosphatase is required to link cell size monitoring to mitotic control. This represents a novel function of the Cdc25 phosphatase. Furthermore, we demonstrate that this cell size-monitoring system fulfills the formal criteria of a cell cycle checkpoint.

scholarly journals Ribosome Biogenesis Is Sensed at the Start Cell Cycle Checkpoint

2007 ◽  
Vol 18 (3) ◽  
pp. 953-964 ◽  
Author(s):  
Kara A. Bernstein ◽  
Franziska Bleichert ◽  
James M. Bean ◽  
Frederick R. Cross ◽  
Susan J. Baserga
Keyword(s):  
Cell Cycle ◽  
Cell Size ◽  
Ribosome Biogenesis ◽  
Human Tumor ◽  
Cell Cycle Checkpoint ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cycle Checkpoint ◽  
Functional Equivalent ◽  
Synthetic Capacity ◽  
Dependent Mechanism

In the yeast Saccharomyces cerevisiae it has long been thought that cells must reach a critical cell size, called the “setpoint,” in order to allow the Start cell cycle transition. Recent evidence suggests that this setpoint is lowered when ribosome biogenesis is slowed. Here we present evidence that yeast can sense ribosome biogenesis independently of mature ribosome levels and protein synthetic capacity. Our results suggest that ribosome biogenesis directly promotes passage through Start through Whi5, the yeast functional equivalent to the human tumor suppressor Rb. When ribosome biogenesis is inhibited, a Whi5-dependent mechanism inhibits passage through Start before significant decreases in both the number of ribosomes and in overall translation capacity of the cell become evident. This delay at Start in response to decreases in ribosome biogenesis occurs independently of Cln3, the major known Whi5 antagonist. Thus ribosome biogenesis may be sensed at multiple steps in Start regulation. Ribosome biogenesis may thus both delay Start by increasing the cell size setpoint and independently may promote Start by inactivating Whi5.

nimO, an Aspergillus gene related to budding yeast Dbf4, is required for DNA synthesis and mitotic checkpoint control

1999 ◽  
Vol 112 (9) ◽  
pp. 1313-1324 ◽  
Author(s):  
S.W. James ◽  
K.A. Bullock ◽  
S.E. Gygax ◽  
B.A. Kraynack ◽  
R.A. Matura ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Budding Yeast ◽  
Hyphal Growth ◽  
Mitotic Checkpoint ◽  
Cell Cycle Checkpoint ◽  
Regulatory Subunit ◽  
Checkpoint Control ◽  
Replication Checkpoint ◽  
C Terminus ◽  
Cycle Checkpoint

The nimO predicted protein of Aspergillus nidulans is related structurally and functionally to Dbf4p, the regulatory subunit of Cdc7p kinase in budding yeast. nimOp and Dbf4p are most similar in their C-termini, which contain a PEST motif and a novel, short-looped Cys2-His2 zinc finger-like motif. DNA labelling and reciprocal shift assays using ts-lethal nimO18 mutants showed that nimO is required for initiation of DNA synthesis and for efficient progression through S phase. nimO18 mutants abrogated a cell cycle checkpoint linking S and M phases by segregating their unreplicated chromatin. This checkpoint defect did not interfere with other checkpoints monitoring spindle assembly and DNA damage (dimer lesions), but did prevent activation of a DNA replication checkpoint. The division of unreplicated chromatin was accelerated in cells lacking a component of the anaphase-promoting complex (bimEAPC1), consistent with the involvement of nimO and APC/C in separate checkpoint pathways. A nimO deletion conferred DNA synthesis and checkpoint defects similar to nimO18. Inducible nimO alleles lacking as many as 244 C-terminal amino acids supported hyphal growth, but not asexual development, when overexpressed in a ts-lethal nimO18 strain. However, the truncated alleles could not rescue a nimO deletion, indicating that the C terminus is essential and suggesting some type of interaction among nimO polypeptides.

Cell Cycle Checkpoint Genes and Aneuploidy: A Short Review

2001 ◽  
Vol 2 (2) ◽  
pp. 171-180 ◽  
Author(s):  
William Kearns ◽  
Johnson Liu
Keyword(s):  
Cell Cycle ◽  
Short Review ◽  
Cell Cycle Checkpoint ◽  
Cycle Checkpoint ◽  
Checkpoint Genes

scholarly journals Acceleration or Brakes: Which Is Rational for Cell Cycle-Targeting Neuroblastoma Therapy?

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 750
Author(s):  
Kiyohiro Ando ◽  
Akira Nakagawara
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Progression ◽  
Parp Inhibitors ◽  
Cell Cycle Checkpoint ◽  
Mitotic Catastrophe ◽  
Malignant Neoplasms ◽  
Checkpoint Kinases ◽  
Molecular Features ◽  
Cycle Checkpoint

Unrestrained proliferation is a common feature of malignant neoplasms. Targeting the cell cycle is a therapeutic strategy to prevent unlimited cell division. Recently developed rationales for these selective inhibitors can be subdivided into two categories with antithetical functionality. One applies a “brake” to the cell cycle to halt cell proliferation, such as with inhibitors of cell cycle kinases. The other “accelerates” the cell cycle to initiate replication/mitotic catastrophe, such as with inhibitors of cell cycle checkpoint kinases. The fate of cell cycle progression or arrest is tightly regulated by the presence of tolerable or excessive DNA damage, respectively. This suggests that there is compatibility between inhibitors of DNA repair kinases, such as PARP inhibitors, and inhibitors of cell cycle checkpoint kinases. In the present review, we explore alterations to the cell cycle that are concomitant with altered DNA damage repair machinery in unfavorable neuroblastomas, with respect to their unique genomic and molecular features. We highlight the vulnerabilities of these alterations that are attributable to the features of each. Based on the assessment, we offer possible therapeutic approaches for personalized medicine, which are seemingly antithetical, but both are promising strategies for targeting the altered cell cycle in unfavorable neuroblastomas.

scholarly journals RSF1 in cancer: interactions and functions

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guiyang Cai ◽  
Qing Yang ◽  
Wei Sun
Keyword(s):  
Optimal Level ◽  
Cell Cycle Checkpoint ◽  
Protein Homeostasis ◽  
Clinical Value ◽  
Cancer Proliferation ◽  
Poor Overall Survival ◽  
Cyclin E1 ◽  
Spacing Factor ◽  
Cycle Checkpoint ◽  
Cancer Types

AbstractRSF1, remodelling and spacing factor 1, is an important interphase centromere protein and is overexpressed in many types of cancers and correlated with poor overall survival. RSF1 has functions mainly in maintaining chromosome stability, facilitating DNA repair, maintaining the protein homeostasis of RSF1 and suppressing the transcription of some oncogenes when RSF1 protein is expressed at an optimal level; however, RSF1 overexpression facilitates drug resistance and cell cycle checkpoint inhibition to prompt cancer proliferation and survival. The RSF1 expression level and gene background are crucial for RSF1 functions, which may explain why RSF1 has different functions in different cancer types. This review summarizes the functional domains of RSF1, the overexpression status of RSF1 and SNF2H in cancer based on the TCGA and GTEX databases, the cancer-related functions of RSF1 in interacting with H2Aub, HDAC1, CENP-A, PLK1, ATM, CENP-S, SNF2H, HBX, BubR1, cyclin E1, CBP and NF-κB and the potential clinical value of RSF1, which will lay a theoretical foundation for the structural biology study of RSF1 and application of RSF1 inhibitors, truncated RSF1 proteins and SNF2H inhibitors in the treatment of RSF1-overexpressing tumours.

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