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Cell Cycle Events (cell + cycle_event)
Selected AbstractsCell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiaeGENES TO CELLS, Issue 6 2006Daniel G. Gibson Chromosomal replication initiates through the assembly of a prereplicative complex (pre-RC) at individual replication origins in the G1-phase, followed by activation of these complexes in the S-phase. In Saccharomyces cerevisiae, the origin recognition complex (ORC) binds replication origins throughout the cell cycle and participates in pre-RC assembly. Whether the ORC plays an additional role subsequent to pre-RC assembly in replication initiation or any other essential cell cycle process is not clear. To study the function of the ORC during defined cell cycle periods, we performed cell cycle execution point analyses with strains containing a conditional mutation in the ORC1, ORC2 or ORC5 subunit of ORC. We found that the ORC is essential for replication initiation, but is dispensable for replication elongation or later cell cycle events. Defective initiation in ORC mutant cells results in incomplete replication and mitotic arrest enforced by the DNA damage and spindle assembly checkpoint pathways. The involvement of the spindle assembly checkpoint implies a defect in kinetochore-spindle attachment or sister chromatid cohesion due to incomplete replication and/or DNA damage. Remarkably, under semipermissive conditions for ORC1 function, the spindle checkpoint alone suffices to block proliferation, suggesting this checkpoint is highly sensitive to replication initiation defects. We discuss the potential significance of these overlapping checkpoints and the impact of our findings on previously postulated role(s) of ORCs in other cell cycle functions. [source] Neurogenesis and cell cycle-reactivated neuronal death during pathogenic tau aggregationGENES, BRAIN AND BEHAVIOR, Issue 2008K. Schindowski The aim of the present study was to investigate the relation between neurogenesis, cell cycle reactivation and neuronal death during tau pathology in a novel tau transgenic mouse line THY-Tau22 with two frontotemporal dementia with parkinsonism linked to chromosome-17 mutations in a human tau isoform. This mouse displays all Alzheimer disease features of neurodegeneration and a broad timely resolution of tau pathology with hyperphosphorylation of tau at younger age (up to 6 months) and abnormal tau phosphorylation and tau aggregation in aged mice (by 10 months). Here, we present a follow-up of cell cycle markers with aging in control and transgenic mice from different ages. We show that there is an increased neurogenesis during tau hyperphosphorylation and cell cycle events during abnormal tau phosphorylation and tau aggregation preceding neuronal death and neurodegeneration. However, besides phosphorylation, other mechanisms including tau mutations and changes in tau expression and/or splicing may be also involved in these mechanisms of cell cycle reactivation. Altogether, these data suggest that cell cycle events in THY-Tau22 are resulting from neurogenesis in young animals and cell death in older ones. It suggests that neuronal cell death in such models is much more complex than believed. [source] Functional potential of P2P-R: A role in the cell cycle and cell differentiation related to its interactions with proteins that bind to matrix associated regions of DNA?JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2003Robert E. Scott Abstract P2P-R is the alternately spliced product of the P2P-R/PACT gene in that P2P-R lacks one exon encoding 34 amino acids. The 250 kDa P2P-R protein is the predominate product expressed in multiple murine cell lines. It is a highly basic protein that contains multiple domains including an N-terminal RING type zinc finger, a proline rich domain, an RS region, and a C-terminal lysine-rich domain. P2P-R binds the p53 and the Rb1 tumor suppressors and is phosphorylated by the cdc2 and SRPK1a protein kinases. P2P-R also interacts with scaffold attachment factor-B (SAF-B), a well characterized MARs (for matrix attachment regions) binding factor, and may interact with nucleolin, another MARs binding factor. In addition, P2P-R binds single strand DNA (ssDNA). The expression of P2P-R is regulated by differentiation and cell cycle events. P2P-R mRNA is markedly repressed during differentiation, whereas immunoreactive P2P-R protein levels are >10-fold higher in mitotic than in G0 cells. The localization of P2P-R also is modulated during the cell cycle. During interphase, P2P-R is present primarily in nucleoli and nuclear speckles whereas during mitosis, P2P-R associates with the periphery of chromosomes. Overexpression of near full length P2P-R induces mitotic arrest in prometaphase and mitotic apoptosis, and overexpression of selected P2P-R segments also can promote apoptosis. This compendium of data supports the possibility that P2P-R may form complexes with the Rb1 and/or p53 tumor suppressors and MARs-related factors, in a cell cycle and cell differentiation-dependent manner, to influence gene transcription/expression and nuclear organization. J. Cell. Biochem. 90: 6,12, 2003. © 2003 Wiley-Liss, Inc. [source] Plasticity of a transcriptional regulation network among alpha-proteobacteria is supported by the identification of CtrA targets in Brucella abortusMOLECULAR MICROBIOLOGY, Issue 4 2002Anne-Flore Bellefontaine Summary CtrA is a master response regulator found in many alpha-proteobacteria. In Caulobacter crescentus and Sinorhizobium meliloti, this regulator is essential for viability and is transcriptionally autoregulated. In C. crescentus, it is required for the regulation of multiple cell cycle events, such as DNA methylation, DNA replication, flagella and pili biogenesis and septation. Here, we report the characterization of the ctrA gene homologue in the ,2 -proteobacteria Brucella abortus, a facultative intracellular pathogen responsible for brucellosis. We detected CtrA expression in the main Brucella species, and its overproduction led to a phenotype typical of cell division defect, consistent with its expected role. A purified B. abortus CtrA recombinant protein (His6,CtrA) was shown to protect the B. abortus ctrA promoter from DNase I digestion, suggesting transcriptional autoregulation, and this protection was enhanced under CtrA phosphorylation on a conserved Asp residue. Despite the similarities shared by B. abortus and C. crescentus ctrA, the pathway downstream from CtrA may be distinct, at least partially, in both bacteria. Indeed, beside ctrA itself, only one (the ccrM gene) out of four B. abortus homologues of known C. crescentus CtrA targets is bound in vitro by phosphorylated B. abortus CtrA. Moreover, further footprinting experiments support the hypothesis that, in B. abortus, CtrA might directly regulate the expression of the rpoD, pleC, minC and ftsE homologues. Taken together, these results suggest that, in B. abortus and C. crescentus, similar cellular processes are regulated by CtrA through the control of distinct target genes. The plasticity of the regulation network involving CtrA in these two bacteria may be related to their distinct lifestyles. [source] Proline-directed phosphorylation and isomerization in mitotic regulation and in Alzheimer's DiseaseBIOESSAYS, Issue 2 2003Kun Ping Lu The reversible phosphorylation of proteins on serine/threonine residues preceding proline (Ser/Thr-Pro) is a major regulatory mechanism for the control of a series of cell cycle events. Although phosphorylation is thought to regulate protein function by inducing conformational changes, little is known about most of these conformational changes and their significance. Recent studies indicate that the conformation and function of a subset of these phosphorylated proteins are controlled by the prolyl isomerase Pin1 through isomerization of specific phosphorylated Ser/Thr-Pro bonds. Furthermore, compelling evidence supports the idea that proline-directed phosphorylation and subsequent isomerization play a critical role not only in cell cycle control, but also in the development of Alzheimer's disease, where postmitotic neurons display various cell cycle markers, especially mitotic events, prior to degeneration. BioEssays 25:174,181, 2003. © 2003 Wiley Periodicals, Inc. [source] | ||||||||||