http://www.celldiv.com The latest research articles published by Cell Division 2012-02-03T00:00:00Z Background: Aneuploidy has been acknowledged as a major source of genomic instability in cancer, and it is often considered the result of chromosome segregation errors including those caused by defects in genes controlling the mitotic spindle assembly, centrosome duplication and cell-cycle checkpoints. Aneuploidy and chromosomal instability has been also correlated with epigenetic alteration, however the molecular basis of this correlation is poorly understood. Results: To address the functional connection existing between epigenetic changes and aneuploidy, we used RNA-interference to silence the DNMT1 gene, encoding for a highly conserved member of the DNA methyl-transferases. DNMT1 depletion slowed down proliferation of near-diploid human tumor cells (HCT116) and triggered G1 arrest in primary human fibroblasts (IMR90), by inducing p53 stabilization and, in turn, p21waf1 transactivation. Remarkably, p53 increase was not caused by DNA damage and was not observed after p14-ARF post-transcriptional silencing. Interestingly, DNMT1 silenced cells with p53 or p14-ARF depleted did not arrest in G1 but, instead, underwent DNA hypomethylation and became aneuploid. Conclusion: Our results suggest that DNMT1 depletion triggers a p14ARF/p53 dependent cell cycle arrest to counteract the aneuploidy induced by changes in DNA methylation. http://www.celldiv.com/content/7/1/2 Viviana Barra Tiziana Schillaci Laura Lentini Giuseppe Costa Aldo Di Leonardo Cell Division 2012, null:2 2012-02-03T00:00:00Z doi:10.1186/1747-1028-7-2 /content/figures/1747-1028-7-2-toc.gif Cell Division 1747-1028 ${item.volume} 2 2012-02-03T00:00:00Z PDF Background: The maintenance of genomic integrity is essential for cell viability. Complex signalling pathways (DNA integrity checkpoints) mediate the response to genotoxic stresses. Identifying new functions involved in the cellular response to DNA-damage is crucial. The Saccharomyces cerevisiae SLT2 gene encodes a member of the mitogen-activated protein kinase (MAPK) cascade whose main function is the maintenance of the cell wall integrity. However, different observations suggest that SLT2 may also have a role related to DNA metabolism. Results: This work consisted in a comprehensive study to connect the Slt2 protein to genome integrity maintenance in response to genotoxic stresses. The slt2 mutant strain was hypersensitive to a variety of genotoxic treatments, including incubation with hydroxyurea (HU), methylmetanosulfonate (MMS), phleomycin or UV irradiation. Furthermore, Slt2 was activated by all these treatments, which suggests that Slt2 plays a central role in the cellular response to genotoxic stresses. Activation of Slt2 was not dependent on the DNA integrity checkpoint. For MMS and UV, Slt2 activation required progression through the cell cycle. In contrast, HU also activated Slt2 in nocodazol-arrested cells, which suggests that Slt2 may respond to dNTP pools alterations. However, neither the protein level of the distinct ribonucleotide reductase subunits nor the dNTP pools were affected in a slt2 mutant strain. An analysis of the checkpoint function revealed that Slt2 was not required for either cell cycle arrest or the activation of the Rad53 checkpoint kinase in response to DNA damage. However, slt2 mutant cells showed an elongated bud and partially impaired Swe1 degradation after replicative stress, indicating that Slt2 could contribute, in parallel with Rad53, to bud morphogenesis control after genotoxic stresses. Conclusions: Slt2 is activated by several genotoxic treatments and is required to properly cope with DNA damage. Slt2 function is important for bud morphogenesis and optimal Swe1 degradation under replicative stress. The MAPK Slt2 appears as a new player in the cellular response to genotoxic stresses. http://www.celldiv.com/content/7/1/1 Maria Soriano-Carot M. Carmen Bano J. Carlos Igual Cell Division 2012, null:1 2012-02-01T00:00:00Z doi:10.1186/1747-1028-7-1 /content/figures/1747-1028-7-1-toc.gif Cell Division 1747-1028 ${item.volume} 1 2012-02-01T00:00:00Z PDF Background: Cdc5 (polo kinase/Plk1) is a highly conserved key regulator of the S. cerevisiae cell cycle from S-phase until cytokinesis. However, much of the regulatory mechanisms that govern Cdc5 remain to be determined. Cdc5 is phosphorylated on up to 10 sites during mitosis. In this study, we investigated the function of phosphorylation site T23, the only full consensus Cdk1 (Cdc28) phosphorylation site present.FindingsCdc5T23A introduces a degron that reduces its cellular amount to undetectable levels, which are nevertheless sufficient for normal cell proliferation. The degron acts in cis and is reversed by N-terminal GFP-tagging. Cdk1 kinase activity is required to maintain Cdc5 levels during G2. This, Cdk1 inhibited, Cdc5 degradation is APC/CCdh1 independent and requires new protein synthesis. Cdc5T23E is hyperactive, and reduces the levels of Cdc5 (in trans) and drastically reduces Clb2 levels. Conclusions: Phosphorylation of Cdc5 by Cdk1 is required to maintain Cdc5 levels during G2. However, phosphorylation of T23 (probably by Cdk1) caps Cdc5 and other CLB2 cluster protein accumulation, preventing potential protein toxicity, which may arise from their overexpression or from APC/CCdh1 inactivation. http://www.celldiv.com/content/6/1/23 Kobi Simpson-Lavy Michael Brandeis Cell Division 2011, null:23 2011-12-28T00:00:00Z doi:10.1186/1747-1028-6-23 /content/figures/1747-1028-6-23-toc.gif Cell Division 1747-1028 ${item.volume} 23 2011-12-28T00:00:00Z XML Background: Multicellular tumor spheroids are models of increasing interest for cancer and cell biology studies. They allow considering cellular interactions in exploring cell cycle and cell division mechanisms. However, 3D imaging of cell division in living spheroids is technically challenging and has never been reported. Results: Here, we report a major breakthrough based on the engineering of multicellular tumor spheroids expressing an histone H2B fluorescent nuclear reporter protein, and specifically designed sample holders to monitor live cell division dynamics in 3D large spheroids using an home-made selective-plane illumination microscope. Conclusions: As illustrated using the antimitotic drug, paclitaxel, this technological advance paves the way for studies of the dynamics of cell divion processes in 3D and more generally for the investigation of tumor cell population biology in integrated system as the spheroid model. http://www.celldiv.com/content/6/1/22 Corinne Lorenzo Celine Frongia Raphael Jorand Jerome Fehrenbach Pierre Weiss Amina Maandhui Guillaume Gay Bernard Ducommun Valerie Lobjois Cell Division 2011, null:22 2011-12-12T00:00:00Z doi:10.1186/1747-1028-6-22 Imaging and 3D reconstruction of interphase and mitotic nuclei within a fixed H2B¿HcRed-expressing spheroid Picture illustrating 3D reconstructions of interphase and mitotic nuclei within a fixed H2B¿HcRed-expressing spheroid. The blue correspond to interphase nuclei and red to mitotic condensed chromosomes. These reconstructions have been obtained from SPIM z-stacks and processed using the VSNR, FIJI and Imaris softwares. /content/figures/1747-1028-6-22-toc.gif Cell Division 1747-1028 ${item.volume} 22 2011-12-12T00:00:00Z PDF Maintenance of genomic integrity is essential for cell survival. Specifically, during DNA replication cells use a complex network of mechanisms that prevents genomic instability. Recently, we and others identified Wee1, a serine/threonine and tyrosine kinase, as a new modulator of the genomic stability during S phase. Loss of its activity causes a general DNA damage response activation and a decrease in replication fork speed. These effects are counteracted by the downregulation of the endonuclease complex Mus81-Eme1, showing a new link between this endonuclease and Wee1 during DNA replication. Here we discuss the function of Wee1 in genomic stability and its relationship with the Mus81-Eme1 complex. http://www.celldiv.com/content/6/1/21 Yuse Martin Raquel Dominguez-Kelly Raimundo Freire Cell Division 2011, null:21 2011-12-09T00:00:00Z doi:10.1186/1747-1028-6-21 53BP1 green fluorescence /content/figures/1747-1028-6-21-toc.gif Cell Division 1747-1028 ${item.volume} 21 2011-12-09T00:00:00Z XML The cell cycle is a tightly controlled series of events that ultimately lead to cell division. The literature deciphering the molecular processes involved in regulating the consecutive cell cycle steps is colossal. By contrast, much less is known about non-dividing cellular states, even if they concern the vast majority of cells, from prokaryotes to multi-cellular organisms. Indeed, cells decide to enter the division cycle only if conditions are favourable. Otherwise they may enter quiescence, a reversible non-dividing cellular state. Recent studies in yeast have shed new light on the transition between proliferation and quiescence, re-questioning the notion of cell cycle commitment. They also indicate a predominant role for cellular metabolic status as a major regulator of quiescence establishment and exit. Additionally, a growing body of evidence indicates that environmental conditions, and notably the availability of various nutrients, by impinging on specific metabolic routes, directly regulate specific cellular re-organization that occurs upon proliferation/quiescence transitions. http://www.celldiv.com/content/6/1/20 Bertrand Daignan-Fornier Isabelle Sagot Cell Division 2011, null:20 2011-12-09T00:00:00Z doi:10.1186/1747-1028-6-20 Quiescent budding yeast markers Quiescent budding yeast cells displaying Actin Bodies (green dots) and Proteasome Storage Granule (red dot). Some proteasome remains at the nuclear membrane. Wild type yeast cells expressing Abp1-GFP and Pup1-RFP were grown 4 days in rich medium and directly imaged. /content/figures/1747-1028-6-20-toc.gif Cell Division 1747-1028 ${item.volume} 20 2011-12-09T00:00:00Z XML Regulation of cytoskeletal remodeling is essential for cell cycle transitions. In fission yeast two NDR kinase signaling cascades, MOR and SIN, regulate the actin cytoskeleton to promote polarized growth during interphase and cytokinesis respectively. Our understanding of how these signaling pathways are coordinated to assist transition between the two cell-cycle stages is limited. Here, we review work from our laboratory, which reveals that cross talk between the SIN and MOR pathways is required for inhibition of interphase polarity programs during cytokinesis. Given the conservation of NDR kinase signaling pathways, our results may define general mechanisms by which these pathways are coordinated in higher organisms. http://www.celldiv.com/content/6/1/19 Sneha Gupta Dannel McCollum Cell Division 2011, null:19 2011-11-11T00:00:00Z doi:10.1186/1747-1028-6-19 /content/figures/1747-1028-6-19-toc.gif Cell Division 1747-1028 ${item.volume} 19 2011-11-11T00:00:00Z XML Early studies in lower Eukaryotes have defined a role for the members of the NimA related kinase (Nek) family of protein kinases in cell cycle control. Expansion of the Nek family throughout evolution has been accompanied by their broader involvement in checkpoint regulation and cilia biology. Moreover, mutations of Nek family members have been identified as drivers behind the development of ciliopathies and cancer. Recent advances in studying the physiological roles of Nek family members utilizing mouse genetics and RNAi-mediated knockdown are revealing intricate associations of Nek family members with fundamental biological processes. Here, we aim to provide a comprehensive account of our understanding of Nek kinase biology and their involvement in cell cycle, checkpoint control and cancer. http://www.celldiv.com/content/6/1/18 Larissa Moniz Previn Dutt Nasir Haider Vuk Stambolic Cell Division 2011, null:18 2011-10-31T00:00:00Z doi:10.1186/1747-1028-6-18 /content/figures/1747-1028-6-18-toc.gif Cell Division 1747-1028 ${item.volume} 18 2011-10-31T00:00:00Z XML Background: An oocyte undergoes two rounds of asymmetric division to generate a haploid gamete and two small polar bodies designed for apoptosis. Chromosomes play important roles in specifying the asymmetric meiotic divisions in the oocytes but the underlying mechanism is poorly understood. Results: Chromosomes independently induce spindle formation and cortical actomyosin assembly into special cap and ring structures in the cortex of the oocyte. The spindle and the cortical cap/ring interact to generate mechanical forces, leading to polar body extrusion. Two distinct force-driven membrane changes were observed during 2nd polar body extrusion: a protrusion of the cortical cap and a membrane invagination induced by an anaphase spindle midzone. The cortical cap protrusion and invagination help rotate the spindle perpendicularly so that the spindle midzone can induce bilateral furrows at the shoulder of the protruding cap, leading to an abscission of the polar body. It is interesting to note that while the mitotic spindle midzone induces bilateral furrowing, leading to efficient symmetric division in the zygote, the meiotic spindle midzone induced cytokinetic furrowing only locally. Conclusions: Distinct forces driving cortical cap protrusion and membrane invagination are involved in spindle rotation and polar body extrusion during meiosis II in mouse oocytes. http://www.celldiv.com/content/6/1/17 Qiong Wang Catherine Racowsky Manqi Deng Cell Division 2011, null:17 2011-08-25T00:00:00Z doi:10.1186/1747-1028-6-17 /content/figures/1747-1028-6-17-toc.gif Cell Division 1747-1028 ${item.volume} 17 2011-08-25T00:00:00Z XML The anaphase promoting complex is a highly conserved E3 ligase complex that mediates the destruction of key regulatory proteins during both mitotic and meiotic divisions. In order to maintain ploidy, this destruction must occur after the regulatory proteins have executed their function. Thus, the regulation of APC/C activity itself is critical for maintaining ploidy during all types of cell divisions. During mitotic cell division, two conserved activator proteins called Cdc20 and Cdh1 are required for both APC/C activation and substrate selection. However, significantly less is known about how these proteins regulate APC/C activity during the specialized meiotic nuclear divisions. In addition, both budding yeast and flies utilize a third meiosis-specific activator. In Saccharomyces cerevisiae, this meiosis-specific activator is called Ama1. This review summarizes our knowledge of how Cdc20 and Ama1 coordinate APC/C activity to regulate the meiotic nuclear divisions in yeast. http://www.celldiv.com/content/6/1/16 Katrina Cooper Randy Strich Cell Division 2011, null:16 2011-08-01T00:00:00Z doi:10.1186/1747-1028-6-16 /content/figures/1747-1028-6-16-toc.gif Cell Division 1747-1028 ${item.volume} 16 2011-08-01T00:00:00Z XML