33 research outputs found
One-hit wonders of genomic instability
No full textAbstract Recent data show that cells from many cancers exhibit massive chromosome instability. The traditional view is that the gradual accumulation of mutations in genes involved in transcriptional regulation and cell cycle controls results in tumor development. This, however, does not exclude the possibility that some mutations could be more potent than others in destabilizing the genome by targeting both chromosomal integrity and corresponding checkpoint mechanisms simultaneously. Three such examples of "single-hit" lesions potentially leading to heritable genome destabilization are discussed. They include: failure to release sister chromatid cohesion due to the incomplete proteolytic cleavage of cohesin; massive merotelic kinetochore misattachments upon condensin depletion; and chromosome under-replication. In all three cases, cells fail to detect potential chromosomal bridges before anaphase entry, indicating that there is a basic cell cycle requirement to maintain a degree of sister chromatid bridging that is not recognizable as chromosomal damage.</p
Cohesin complexes with a potential to link mammalian meiosis to cancer
No full textAmong multiple genes aberrantly activated in cancers, invariably, there is a group related to the capacity of cell to self-renewal. Some of these genes are related to the normal process of development, including the establishment of a germline. This group, a part of growing family of Cancer/Testis (CT) genes, now includes the meiosis specific subunits of cohesin complex. The first reports characterizing the SMC1 and RAD21 genes, encoding subunits of cohesin, were published 20 years ago; however the exact molecular mechanics of cohesin molecular machine in vivo remains rather obscure notwithstanding ample elegant experiments. The matters are complicated by the fact that the evolution of cohesin function, which is served by just two basic types of protein complexes in budding yeast, took an explosive turn in Metazoa. The recent characterization of a new set of genes encoding cohesin subunits specific for meiosis in vertebrates adds several levels of complexity to the task of structure-function analysis of specific cohesin pathways, even more so in relation to their aberrant functionality in cancers. These three proteins, SMC1β, RAD21L and STAG3 are likely involved in a specific function in the first meiotic prophase, genetic recombination, and segregation of homologues. However, at present, it is rather challenging to pinpoint the molecular role of these proteins, particularly in synaptonemal complex or centromere function, due to the multiplicity of different cohesins in meiosis. The roles of these proteins in cancer cell physiology, upon their aberrant activation in tumors, also remain to be elucidated. Nevertheless, as the existence of Cancer/Testis cohesin complexes in tumor cells appears to be all but certain, this brings a promise of a new target for cancer therapy and/or diagnostics
Study on genes controlling distribution of chromosomes and minichromosomes in mitoses of yeast-saccharomyces
No full textThe study deals with processes of capture, accumulation and gas evolution of ion-introduced deuterium by FR-materials. The work is aimed at determining quantitative characteristics of capture and reemission of ion-introduced deuterium in the energy range of ions typical for FR; comparison estimate of applicability of austenitic and ferritic steels relative to hydrogen recycling in thermonuclear plants. A simple model to describe introduction of low-energy ions with regard to the reflection coefficient and the formula relating the recycling parameter, reflection coefficient, fluence and amount of captured particles are proposed. Angular and energy dependences of the coefficients of capture and reflection in the energy range of 10-30 eV/deuton for tungsten and steel are first measured experimentally. Non-monotonous dependence of the coefficient of capture and reflection on particle energy is determined experimentally for a tangent angle of incidenceAvailable from VNTIC / VNTIC - Scientific & Technical Information Centre of RussiaSIGLERURussian Federatio
MITOTIC CHROMOSOME CONDENSATION
No full text ▪ Abstract In this chapter, we review the structure and composition of interphase and mitotic chromosomes. We discuss how these observations support the model that mitotic condensation is a deterministic process leading to the invariant folding of a given chromosome. The structural studies have also placed constraints on the mechanism of condensation and defined several activities needed to mediate condensation. In the context of these activities and structural information, we present our current understanding of the role of cis sites, histones, topoisomerase II, and SMC proteins in condensation. We conclude by using our current knowledge of mitotic condensation to address the differences in chromosome condensation observed from bacteria to humans and to explore the relevance of this process to other processes such as gene expression. </jats:p
A Direct Link between Sister Chromatid Cohesion and Chromosome Condensation Revealed through the Analysis of MCD1 in S. cerevisiae
No full textAbstractThe S. cerevisiae MCD1(mitotic chromosome determinant) gene was identified in genetic screens for genes important for chromosome structure. MCD1 is essential for viability and homologs are found from yeast to humans. Analysis of the mcd1 mutant and cell cycle–dependent expression pattern of Mcd1p suggest that this protein functions in chromosome morphogenesis from S phase through mitosis. The mcd1 mutant is defective in sister chromatid cohesion and chromosome condensation. The physical association between Mcd1p and Smc1p, one of the SMC family of chromosomal proteins, further suggests that Mcd1p functions directly on chromosomes. These data implicate Mcd1p as a nexus between cohesion and condensation. We present a model for mitotic chromosome structure that incorporates this previously unsuspected link
Functional dissection of in vivo interchromosome association in Saccharomyces cerevisiae
No full text
Subcellular localization of Bacillus subtilis SMC, a protein involved in chromosome condensation and segregation
No full textWe have investigated the subcellular localization of the SMC protein in the gram-positive bacterium Bacillus subtilis. Recent work has shown that SMC is required for chromosome condensation and faithful chromosome segregation during the B. subtilis cell cycle. Using antibodies against SMC and fluorescence microscopy, we have shown that SMC is associated with the chromosome but is also present in discrete foci near the poles of the cell. DNase treatment of permeabilized cells disrupted the association of SMC with the chromosome but not with the polar foci. The use of a truncated smc gene demonstrated that the C-terminal domain of the protein is required for chromosomal binding but not for the formation of polar foci. Regular arrays of SMC-containing foci were still present between nucleoids along the length of aseptate filaments generated by depleting cells of the cell division protein FtsZ, indicating that the formation of polar foci does not require the formation of septal structures. In slowly growing cells, which have only one or two chromosomes, SMC foci were principally observed early in the cell cycle, prior to or coincident with chromosome segregation. Cell cycle-dependent release of stored SMC from polar foci may mediate segregation by condensation of chromosomes. A significant unsolved problem in the biology of bacteria is the nature of the machinery that is responsible for the segre-gation of daughter chromosomes with high fidelity during th
