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Identification of and mutational studies conducted on the gene DHC1 reveal that it encodes a dynein heavy chain isoform within the Saccharomyces cerevisiae. Sequence analysis of a 9-kb genomic fragment of the DHC1 gene yielded four polypeptides closely resembling the dynein sequences derived from the sea urchin, Dictyostelium, Drosophila and rat. The dynein microtubule motor protein has an unimportant role in spindle assembly in yeast. However, it has a vital role in regulating spindle orientation in the course of cell division.

DNA double-strand breaks arise in vivo when a dicentric chromosome (two centromeres on one chromosome) goes through mitosis with the two centromeres attached to opposite spindle pole bodies. Repair of the DSBs generates phenotypic diversity due to the range of monocentric derivative chromosomes that arise. To explore whether DSBs may be differentially repaired as a function of their spatial position in the chromosome, we have examined the structure of monocentric derivative chromosomes from cells containing a suite of dicentric chromosomes in which the distance between the two centromeres ranges from 6.5 kb to 57.7 kb. Two major classes of repair products, homology-based (homologous recombination (HR) and single-strand annealing (SSA)) and end-joining (non-homologous (NHEJ) and micro-homology mediated (MMEJ)) were identified. The distribution of repair products varies as a function of distance between the two centromeres. Genetic dependencies on double strand break repair (Rad52), DNA ligase (Lif1), and S phase checkpoint (Mrc1) are indicative of distinct repair pathway choices for DNA breaks in the pericentromeric chromatin versus the arms. Author summary: A challenge in chromosome biology is to integrate the linear code with spatial organization and chromosome dynamics within the nucleus. The major sub-division of function in the nucleus is the nucleolus, the site of ribosomal RNA synthesis. We report that the pericentromere DNA surrounding the centromere is another region of confined biochemistry. We have found that chromosome breaks between two centromeres that both lie within the pericentromeric region of the chromosomes are repaired via pathways that do not rely on sequence homology (MMEJ or NHEJ). Chromosome breaks in dicentric chromosomes whose centromeres are separated by > 20 kb are repaired via pathways that rely mainly on sequence homology (HR, SSA). The repair of breaks in the pericentromere versus breaks in the arms are differentially dependent on Rad52, Lif1, and Mrc1, further indicative of spatial control over DNA repair pathways. [ABSTRACT FROM AUTHOR]

Anaphase onset is an irreversible cell cycle transition that is triggered by the activation of the protease Separase. Separase cleaves the Mcd1 (also known as Scc1) subunit of Cohesin, a complex of proteins that physically links sister chromatids, triggering sister chromatid separation. Separase is regulated by the degradation of the anaphase inhibitor Securin which liberates Separase from inhibitory Securin/Separase complexes. In many organisms, Securin is not essential suggesting that Separase is regulated by additional mechanisms. In this work, we show that in budding yeast Cdk1 activates Separase (Esp1 in yeast) through phosphorylation to trigger anaphase onset. Esp1 activation is opposed by protein phosphatase 2A associated with its regulatory subunit Cdc55 (PP2ACdc55) and the spindle protein Slk19. Premature anaphase spindle elongation occurs when Securin (Pds1 in yeast) is inducibly degraded in cells that also contain phospho-mimetic mutations in ESP1, or deletion of CDC55 or SLK19. This striking phenotype is accompanied by advanced degradation of Mcd1, disruption of pericentric Cohesin organization and chromosome mis-segregation. Our findings suggest that PP2ACdc55 and Slk19 function redundantly with Pds1 to inhibit Esp1 within pericentric chromatin, and both Pds1 degradation and Cdk1-dependent phosphorylation of Esp1 act together to trigger anaphase onset. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To describe the epidemiology of injuries related to cribs, playpens, and bassinets among young children in the United States. METHODS: A retrospective analysis was done using data from the National Electronic Injury Surveillance System for children younger than 2 years of age treated in emergency departments in the United States from 1990 through 2008 for an injury associated with cribs, playpens, and bassinets. RESULTS: An estimated 181 654 (95% confidence interval: 148 548- 214 761) children younger than 2 years of age were treated in emergency departments in the United States for injuries related to cribs, playpens, and bassinets during the 19-year study period. There was an average of 9561 cases per year or an average of 12.1 injuries per 10 000 children younger than 2 years old per year. Most of the injuries involved cribs (83.2%), followed by playpens (12.6%) and bassinets (4.2%). The most common mechanism of injury was a fall from a crib, playpen, or bassinet, representing 66.2% of injuries. Soft-tissue injuries comprised the most common diagnosis (34.1%), and the most frequently injured body region was the head or neck (40.3%). Patients with fractures were admitted 14.0% of the time, makingthem 5.45 (95% confidence interval: 3.80-7.80) times more likely to be hospitalized than patients with other types of injury. Children younger than 6 months were 2.97 (95% confidence interval: 2.07-4.24) times more likely to be hospitalized than older children. CONCLUSIONS: This study is the first to use a nationally representative sample to examine injuries associated with cribs, playpens, and bassinets. Given the consistently high number of observed injuries, greater efforts are needed to ensure safety in the design and manufacture of these products, ensure their proper usage in the home, and increase awareness of their potential dangers to young children. Pediatrics 2011;127:479-486 [ABSTRACT FROM AUTHOR]

With a single microtubule attachment, budding-yeast kinetochores provide an excellent system for understanding the coordinated linkage to dynamic microtubule plus ends for chromosome oscillation and positioning. Fluorescent tagging of kinetochore proteins indicates that, on average, all centromeres are clustered, distinctly separated from their sisters, and positioned equidistant from their respective spindle poles during metaphase. However, individual fluorescent chromosome markers near the centromere transiently reassociate with their sisters and oscillate from one spindle half to the other. To reconcile the apparent disparity between the average centromere position and individual centromere proximal markers, we utilized fluorescence recovery after photobleaching to measure stability of the histone-H3 variant Cse4p/CENP-A. Newly synthesized Cse4p replaces old protein during DNA replication. Once assembled, Cse4-GFP is a physically stable component of centromeres during mitosis. This allowed us to follow centromere dynamics within each spindle half. Kinetochores remain stably attached to dynamic microtubules and exhibit a low incidence of switching orientation or position between the spindle halves. Switching of sister chromatid attachment may be contemporaneous with Cse4p exchange and early kinetochore assembly during S phase; this would promote mixing of chromosome attachment to each spindle pole. Once biorientation is attained, centromeres rarely make excursions beyond their proximal half spindle. [Copyright &y& Elsevier]

Examines the single-strand annealing repair of a dicentric chromosomes in Saccharomyces cerevisiae in nuclear oscillations and nuclear filament formation. Deletion of one centromere via a RAD52-dependent recombination pathway; Changes in nuclear morphology; Suppression of the frequency of spontaneous direct repeat recombination.

Four problems characterize much of the past research on the relation of social factors to juvenile delinquency: measurement of social background, one-dimensional indexes of delinquency, bias in measurement of delinquency, and nonparametric statistical tests. These problems may be overcome in part by using specific, proximal measures of background; multiple indexes of delinquency; anonymous self-reports of delinquency incidence; and parametric statistics such as components analysis and regression or analysis of variance. The present paper demonstrates the use of these methods in a pilot study of about 400 public high-school students in Chicago. The components analysis shows the factor pattern of delinquency varies in samples of boys and girls; hence multiple rather than single indicators must be used. The regression analysis shows that different types of delinquency are functions of different combinations of family background, ethnicity, and sex; for example, boys, especially white boys, in the sample more often reported car thefts; and Negro girls reported more frequently than white girls of having engaged in gang fights. Several methodological implications are drawn from the findings for future research on delinquency. [ABSTRACT FROM AUTHOR]

The article offers information about 2 micron circle, a small circular plasmid with chromosome segregation machinery that ensure its own propagation. The endogenous plasmid 2 micron confers no apparent selective advantage to the host. The harbours of 2 micron has two distinct mechanism that ensure safe passage on each cell division. The chromosome segregation is a microtubule-based that relies on random search and capture process of all the chromosomes.

The centromere is the DNA locus that dictates kinetochore formation and is visibly apparent as heterochromatin that bridges sister kinetochores in metaphase. Sister centromeres are compacted and held together by cohesin, condensin, and topoisomerase-mediated entanglements until all sister chromosomes bi-orient along the spindle apparatus. The establishment of tension between sister chromatids is essential for quenching a checkpoint kinase signal generated from kinetochores lacking microtubule attachment or tension. How the centromere chromatin spring is organized and functions as a tensiometer is largely unexplored. We have discovered that centromere chromatin loops generate an extensional/poleward force sufficient to release nucleosomes proximal to the spindle axis. This study describes how the physical consequences of DNA looping directly underlie the biological mechanism for sister centromere separation and the spring-like properties of the centromere in mitosis. [ABSTRACT FROM AUTHOR]

Summary: The budding yeast kinetochore is ∼68 nm in length with a diameter slightly larger than a 25 nm microtubule [1]. The kinetochores from the 16 chromosomes are organized in a stereotypic cluster encircling central spindle microtubules. Quantitative analysis of the inner kinetochore cluster (Cse4, COMA) reveals structural features not apparent in singly attached kinetochores. The cluster of Cse4-containing kinetochores is physically larger perpendicular to the spindle axis relative to the cluster of Ndc80 molecules [2]. If there was a single Cse4 (molecule or nucleosome) at the kinetochore attached to each microtubule plus end, the cluster of Cse4 would appear geometrically identical to Ndc80. Thus, the structure of the inner kinetochore at the surface of the chromosomes remains unsolved. We have used point fluorescence microscopy and statistical probability maps [2] to deduce the two-dimensional mean position of representative components of the yeast kinetochore relative to the mitotic spindle in metaphase. Comparison of the experimental images to three-dimensional architectures from convolution of mathematical models reveals a pool of Cse4 radially displaced from Cse4 at the kinetochore and kinetochore microtubule plus ends. The pool of displaced Cse4 can be experimentally depleted in mRNA processing pat1Δ or xrn1Δ mutants. The peripheral Cse4 molecules do not template outer kinetochore components. This study suggests an inner kinetochore plate at the centromere-microtubule interface in budding yeast and yields information on the number of Ndc80 molecules at the microtubule attachment site. [Copyright &y& Elsevier]