Horizontal gene transfer: You are what you eat

Horizontal or lateral gene transfer is an effective mechanism for the exchange of genetic information in bacteria allowing bacterial diversification and facilitating adaptation to new environments. Recent data demonstrate that DNA may also be transferred between somatic cells via the uptake of apoptotic bodies. This process allows transfer of viral genes that have been incorporated into the genome in a receptor-independent fashion. Transferred DNA is replicated and propagated in daughter cells in cell that have an inactivated DNA response which may impact tumor progression.     

The problem of transition from the chemical to the biological evolution: some possible solutions

On the basis of evidence that several low-molecular-weight substances as well as enzymes are compartmentalised within the so-called soluble phase of the cell, and other considerations, it is argued that DNA may not contain information for certain types of organisation found in living cells. It may be necessary for a cell to possess the "non-DNA-controlled" organisation for performance of its minimum functions; such organisation would then also serve as a "template" for its appearance in the daughter cell. The problem of transition from chemical to biological evolution (that is, the formation of the "first cell") may be essentially the problem of emergence of such intracellular organisation for which information may not reside in DNA. Two possible mechanisms through which this may have happened are stated.     

Yeast mother cell-specific ageing, genetic (in)stability, and the somatic mutation theory of ageing

Yeast mother cell-specific ageing is characterized by a limited capacity to produce daughter cells. The replicative lifespan is determined by the number of cell cycles a mother cell has undergone, not by calendar time, and in a population of cells its distribution follows the Gompertz law. Daughter cells reset their clock to zero and enjoy the full lifespan characteristic for the strain. This kind of replicative ageing of a cell population based on asymmetric cell divisions is investigated as a model for the ageing of a stem cell population in higher organisms. The simple fact that the daughter cells can reset their clock to zero precludes the accumulation of chromosomal mutations as the cause of ageing, because semiconservative replication would lead to the same mutations in the daughters. However, nature is more complicated than that because, (i) the very last daughters of old mothers do not reset the clock; and (ii) mutations in mitochondrial DNA could play a role in ageing due to the large copy number in the cell and a possible asymmetric distribution of damaged mitochondrial DNA between mother and daughter cell. Investigation of the loss of heterozygosity in diploid cells at the end of their mother cell-specific lifespan has shown that genomic rearrangements do occur in old mother cells. However, it is not clear if this kind of genomic instability is causative for the ageing process. Damaged material other than DNA, for instance misfolded, oxidized or otherwise damaged proteins, seem to play a major role in ageing, depending on the balance between production and removal through various repair processes, for instance several kinds of proteolysis and autophagy. We are reviewing here the evidence for genetic change and its causality in the mother cell-specific ageing process of yeast.     

Septins: traffic control at the cytokinesis intersection

The physical division of one cell into two requires the highly orchestrated separation of genetic and cytoplasmic contents during M phase of the cell cycle. Mitosis, the physical segregation of the genetic material of a cell into two daughter cells, has traditionally received more attention than cytokinesis, the partitioning of the cytoplasmic contents, yet clearly the two processes must be intimately co-ordinated and tightly regulated. While plant cells divide by the formation of a membranous cell barrier called the phragmoplast, animal cell division is largely driven by contraction of an actomyosin ring. However, recent evidence has suggested that membranes derived from one or more intracellular compartments are also required to break the cytoplasmic bridge connecting two dividing cells during late telophase. In this review, we focus on studies of animal cell cytokinesis that support a requirement for specific endomembrane fusion during fission, define molecular components of the membrane fusion apparatus that may be involved and point to possible roles for an emerging family of cytoskeletal proteins, the septins, in this process.     

Studies on the Macronuclei of Doublet Paramecium tetraurelia: Distribution of Macronuclei and DNA at Fission*

SYNOPSIS. Doublet Paramecium tetraurelia would be expected to contain 2 macronuclei if their nuclear complement were strictly analogous to that of singlets. However, most doublets are unimacronucleate. It is shown in this study that dimacronucleate cells are present only in young clones. Unimacronucleate cells arise either through abnormalities in the determination and distribution of macronuclear anlagen during the first cell cycle after conjugation, or from dimacronucleate cells through abnormal division and segregation of macronuclei during the fission process. When a change in the number of macronuclei occurs through abnormalities in the division and segregation of daughter macronuclei, the daughter cells produced typically have DNA contents more similar than those expected from either random segregation of daughter macronuclei, or from the normal segregation pattern in ciliates in which changes in the number of macronuclei in progeny cells do not occur. This suggests that part of the regulation process of macronuclear DNA content in Paramecium may occur through control of the segregation pattern of daughter macronuclei.     

Ultrastructure of cell wall of the cps8 actin mutant cell in Schizosaccharomyces pombe

A Schizosaccharomyces pombe cps8 mutant, of which the gene encodes a mutant actin with an amino acid substitution of Asp for Gly(273) [J. Ishiguro and W. Kobayashi (1996) FEBS Lett. 392, 237-241], was used to determine the role of the actin cytoskeleton in cell wall formation. In the cps8 mutant cells, atomic force microscopic and scanning electron microscopic images showed abnormal depolarized and branched morphology. Fibrous material covered a part of the surface of growing cps8 cells. Transmission electron microscopic images showed variable thickness of the cell wall due to multilayering of cell wall materials, and aberrant multisepta due to diagonal growth of the primary septum, whereas the normal primary septum grows at a right angle from the cortex. This abnormal septum formation may induce abnormality of the cell with multinuclei and/or multisepta, caused by non-separation of daughter cells. These results indicate that actin plays an important role in cell wall and septum formation.     

Cytokinesis: relative alignment of the cell division apparatus and the mitotic spindle

The cell division apparatus is assembled at different stages of the cell cycle in different eukaryotic organisms. Mechanisms exist in all organisms, however, to ensure that the cell division apparatus and the mitotic spindle are aligned perpendicular to each other. Such an alignment ensures that each daughter cell receives a nucleus and that the cell division apparatus does not cleave and destroy the genetic material. The interaction(s) of astral microtubules with the cell cortex appears to play an important role in establishing perpendicularity between chromosome segregation and cell division machinery.     

Nir2, a human homolog of Drosophila melanogaster retinal degeneration B protein,is essential for cytokinesis

Cytokinesis, the final stage of eukaryotic cell division, ensures the production of two daughter cells. It requires fine coordination between the plasma membrane and cytoskeletal networks, and it is known to be regulated by several intracellular proteins, including the small GTPase Rho and its effectors. In this study we provide evidence that the protein Nir2 is essential for cytokinesis. Microinjection of anti-Nir2 antibodies into interphase cells blocks cytokinesis, as it results in the production of multinucleate cells. Immunolocalization studies revealed that Nir2 is mainly localized in the Golgi apparatus in interphase cells, but it is recruited to the cleavage furrow and the midbody during cytokinesis. Nir2 colocalizes with the small GTPase RhoA in the cleavage furrow and the midbody, and it associates with RhoA in mitotic cells. Its N-terminal region, which contains a phosphatidylinositol transfer domain and a novel Rho-inhibitory domain (Rid), is required for normal cytokinesis, as overexpression of an N-terminal-truncated mutant blocks cytokinesis completion. Time-lapse videomicroscopy revealed that this mutant normally initiates cytokinesis but fails to complete it, due to cleavage furrow regression, while Rid markedly affects cytokinesis due to abnormal contractility. Rid-expressing cells exhibit aberrant ingression and ectopic cleavage sites; the cells fail to segregate into daughter cells and they form a long unseparated bridge-like cytoplasmic structure. These results provide new insight into the cellular functions of Nir2 and introduce it as a novel regulator of cytokinesis.     

rough deal: a gene required for proper mitotic segregation in Drosophila

We describe a genetic locus rough deal (rod) in Drosophila melanogaster, identified by mutations that interfere with the faithful transmission of chromosomes to daughter cells during mitosis. Five mutant alleles were isolated, each associated with a similar set of mitotic abnormalities in the dividing neuroblasts of homozygous mutant larvae: high frequencies of aneuploid cells and abnormal anaphase figures, in which chromatids may lag, form bridges, or completely fail to separate. Surviving homozygous adults are sterile, and show cuticular defects associated with cell death, i.e., roughened eyes, sparse abdominal bristles, and notched wing margins. The morphological process of spermatogenesis is largely unaffected and motile sperm are produced, but meiocyte aneuploidy is common. The nature of the observed abnormalities in mitotic cells suggests that the reduced fidelity of chromosome transmission to the daughter cells is due to a failure in a mechanism involved in assuring the proper release of sister chromatids.     

Chromosome segregation in<Emphasis Type="Italic">Bacillus subtilis</Emphasis>

Bacillus subtilis, a Gram-positive bacterium commonly found in soil, is an excellent model organism for the study of basic cell processes, such as cell division and cell differentiation, called sporulation. In B. subtilis the essential genetic information is carried on a single circular chromosome, the correct segregation of which is crucial for both vegetative growth and sporulation. The proper completion of life cycle requires each daughter cell to obtain identical genetic information. The consequences of inaccurate chromosome segregation can lead to formation of anucleate cells, cells with two chromosomes, or cells with incomplete chromosomes. Although bacteria miss the classical eukaryotic mitotic apparatus, the chromosome segregation is undeniably an active process tightly connected to other cell processes as DNA replication and compaction. To fully understand the chromosome segregation, it is necessary to study this process in a wider context and to examine the role of different proteins at various cell life cycle stages. The life cycle of B. subtilis is characteristic by its specific cell differentiation process where, two slightly different segregation mechanisms exist, specialized in vegetative growth and in sporulation.     

DNA replication stress: Causes,resolution and disease

DNA replication is a fundamental process of the cell that ensures accurate duplication of the genetic information and subsequent transfer to daughter cells. Various pertubations, originating from endogenous or exogenous sources, can interfere with proper progression and completion of the replication process, thus threatening genome integrity. Coordinated regulation of replication and the DNA damage response is therefore fundamental to counteract these challenges and ensure accurate synthesis of the genetic material under conditions of replication stress. In this review, we summarize the main sources of replication stress and the DNA damage signaling pathways that are activated in order to preserve genome integrity during DNA replication. We also discuss the association of replication stress and DNA damage in human disease and future perspectives in the field.     

Error propagation in intracellular information transfer

The translation of genetic information from polynucleotides to proteins is mediated by proteins themselves. The cyclic nature of this process admits the possibility of a feedback of errors which may become lethal to the cell. During ageing, it is known that cells in some organisms show increased levels of altered or defective protein, and it has been suggested that the propagation of macromolecular errors may play a causative role in the progressive loss of homeostasis with increasing age. Experimental studies of this hypothesis have so far been inconclusive, and it is shown that theoretical models of intracellular error propagation throw important light on the determinants of stability within the translation apparatus and can improve the design of future experiments, as well as aid in their interpretation.Critical features of any model are its assumptions about the amino acid sequence changes required for a component of the translation apparatus to become error-prone and about the magnitude of any resultant change in activity. Existing models, which differ in these respects, are critically compared, and one is shown to be more flexible than the rest. In common with others, this model predicts that a normally stable translation apparatus has a threshold error level above which stability cannot be regained. The risk of crossing onto an irreversible path to cell death is determined by the distance between the stable and threshold error levels, and experiments to estimate this “safety margin” are suggested. Evolutionary modification of translational stability is also discussed.     

Maintenance of genetic information in stem cells

The available data on DNA cosegregation in some stem cells are reviewed. Cairns was the first to assume cosegregation of template DNA strands for adult stem cells; i.e., all maternal DNA strands are preserved in one daughter cell, which remains a stem cell, while the newly synthesized DNA strands, which may contain errors, appear in the daughter cell that is committed to differentiation and passes to the transitory compartment of the cell population. The role of asymmetric mitosis in DNA cosegregation and maintenance of genetic information in stem cells is discussed.     

Maintenance of genetic information in stem cells

The available data on DNA cosegregation in some stem cells are reviewed. Cairns was the first to assume cosegregation of template DNA strands for adult stem cells; i.e., all maternal DNA strands are preserved in one daughter cell, which remains a stem cell, while the newly synthesized DNA strands, which may contain errors, appear in the daughter cell that is committed to differentiation and passes to the transitory compartment of the cell population. The role of asymmetric mitosis in DNA cosegregation and maintenance of genetic information in stem cells is discussed.     

Unequal cell division and chromatin differentiation in pollen grain cells

Pinus pollen grains, normally developing, were subjected to centrifugal force, low temperature and caffeine solution. In the former two treatments, daughter cells with some abnormal directions of division, abnormal volume and chromatin dispersion were induced in pollen grains treated. Regardless of the direction of division, of the two daughter cells produced by the unequal division, the larger one contained strongly dispersed chromatin and the smaller one weakly dispersed chromatin. In the two daughter cells produced by approximately equal division, the chromatin was dispersed strongly to a similar degree, and by halfway unequal division, chromatin in the larger cell was dispersed strongly and in the smaller one intermediately. Chromatin in bi-nucleate cells induced by caffeine treatment was dispersed strongly to an identical degree. It is suggested that for the occurrence of heteronomous chromatin configuration in natural pollen grains the unequal cell division was indispensable, although the axis of division didn't directly contribute. After both the treatments of centrifugation and low temperature during microspore and embryonal cell divisions, the affected daughter cells divided in terms of the certain fixed axis of division and chromatin dispersion, instead of exhibiting abnormal development.     

鸡心李胚囊及受精的观察

鸡心李(ycopodium cernuum Marsh var.)胚囊发育多数不正常。卵器,极核,反足细胞的数目和在胚囊内的部位有不正常。卵器细胞核,极核,反足细胞核的结构动态有不正常。核物质有穿出现象。受精作用多数不正常。进入胚囊的精子数目、大小、形态、结构有差异。精子有蝌蚪形者,可能有利于主动运动。有单精受精,多精进入卵器或单极核受精。精子染色质有穿出现象。胚囊发育不正常,精子不正常,受精作用不正常,导致败育,果仁腐烂,果实早落。防治方法建议用人工引变,改进遗传性状。     

Fragmentation and partitioning of the Golgi apparatus during mitosis in HeLa cells.

Osmium impregnation was used to determine the number of Golgi apparatus in both interphase and mitotic HeLa cells. The number was found to increase substantially during mitosis to the point where random partitioning alone would explain the nearly equal numbers found in each daughter cell.     

Control of plant cytokinesis by an NPK1-mediated mitogen-activated protein kinase cascade

Cytokinesis is the last essential step in the distribution of genetic information to daughter cells and partition of the cytoplasm. In plant cells, various proteins have been found in the phragmoplast, which corresponds to the cytokinetic apparatus, and in the cell plate, which corresponds to a new cross wall, but our understanding of the functions of these proteins in cytokinesis remains incomplete. Reverse genetic analysis of NPK1 MAPKKK (nucleus- and phragmoplast-localized protein kinase 1 mitogen-activated protein kinase kinase kinase) and investigations of factors that might be functionally related to NPK1 have helped to clarify new aspects of the mechanisms of cytokinesis in plant cells. In this review, we summarize the evidence for the involvement of NPK1 in cytokinesis. We also describe the characteristics of a kinesin-like protein and the homologue of a mitogen-activated protein kinase that we identified recently, and we discuss possible relationships among these proteins in cytokinesis.     

银杏雄配子体发生发育过程中的细胞分裂

银杏（ＧｉｎｋｇｏｂｉｌｏｂａＬ．）小孢子母细胞减数分裂中,拟核经过规律性的变化后,初步建立了由近极面到远极面间的轴向极性,因而,雄配子体萌发时的３次分裂都是典型的极性平周分裂;这些极性平周分裂很可能是对原有极性的进一步加强;在结构上,各子细胞间的细胞壁缺少胞间连丝,因而,这些细胞壁可能起着使子细胞孤立化的作用,从而完成雄配子体中各细胞间的精细分化。生殖细胞的分裂很可能是斜背式环形分裂（ａｎｔｉｃｌｉｎａｌｒｉｎｇｌｉｋｅｄｉｖｉｓｉｏｎ）,这种分裂可能是对最初极性方向的重大调整。结果,精原细胞的分裂方向为垂周分裂,产生两个背靠背排列的精子。     

The Aurora/Ipl1p kinase family: regulators of chromosome segregation and cytokinesis.

Members of the Aurora/Ipl1p family of mitotically regulated serine/threonine kinases are emerging as key regulators of chromosome segregation and cytokinesis. Proper chromosome segregation and cytokinesis ensure that each daughter cell receives the full complement of genetic material. Defects in these processes can lead to aneuploidy and the propagation of genetic abnormalities. This review discusses the Aurora/Ipl1p kinases in terms of their protein structure and proposed function in mitotic cells and also the potential role of aurora2 in human cancer.