Polar Chromosomes - Challenges of a Risky Path

The process of chromosome congression and alignment is at the core of mitotic fidelity. In this review, we discuss distinct spatial routes that the chromosomes take to align during prometaphase, which are characterized by distinct biomolecular requirements. Peripheral polar chromosomes are an intriguing case as their alignment depends on the activity of kinetochore motors, polar ejection forces, and a transition from lateral to end-on attachments to microtubules, all of which can result in the delayed alignment of these chromosomes. Due to their undesirable position close to and often behind the spindle pole, these chromosomes may be particularly prone to the formation of erroneous kinetochore-microtubule interactions, such as merotelic attachments. To prevent such errors, the cell employs intricate mechanisms to preposition the spindle poles with respect to chromosomes, ensure the formation of end-on attachments in restricted spindle regions, repair faulty attachments by error correction mechanisms, and delay segregation by the spindle assembly checkpoint. Despite this protective machinery, there are several ways in which polar chromosomes can fail in alignment, mis-segregate, and lead to aneuploidy. In agreement with this, polar chromosomes are present in certain tumors and may even be involved in the process of tumorigenesis

On the Zagreb Indices as Complexity Indices

Two original Zagreb indices, denoted M1 and M2, and introduced in 1972, were symmetry-modified by summing up only degrees (SMM1) or edge-weights (SMM2) of symmetry nonequivalent vertices or edges of graphs. Their dependence on the structural features and symmetry of molecular graphs is studied. They were also compared to eight other complexity indices (RCI, TC, TC1, BT, BI, twc, wcx) on nine graphs (A, B, C, D, E, F, G, H, I) with five vertices that were earlier studied by several research groups. The TC, TC1 and Nt produce exactly the same complexity ordering of nine graphs (I>H>G>F>E>D>C>B>A). The ordering produced by M1 is different from this ordering in that it cannot discriminate E and F, and C and D. Likewise, M2 and twc produce exactly the same ordering and the latter ordering differs from the former only in the reverse order of E and F. Orderings produced by SMM1 and SMM2 differ considerably from orderings given by TC, TC1 and Nt or M2 and twc

Single-molecule imaging of cytoplasmic dynein in vivo

While early fluorescence microscopy experiments employing fluorescent probes afforded snapshots of the cell, the power of live-cell microscopy is required to understand complex dynamics in biological processes. The first successful cloning of green fluorescent protein in the 1990s paved the way for development of approaches that we now utilize for visualization in a living cell. In this chapter, we discuss a technique to observe fluorescently tagged single molecules in fission yeast. With a few simple modifications to the established total internal reflection fluorescence microscopy, cytoplasmic dynein molecules in the cytoplasm and on the microtubules can be visualized and their intracellular dynamics can be studied. We illustrate a technique to study motor behavior, which is not apparent in conventional ensemble studies of motors. In general, this technique can be employed to study single-molecule dynamics of fluorescently tagged proteins in the cell interior

Asymmetric damage segregation at cell division via protein aggregate fusion and attachment to organelles

The segregation of damaged components at cell division determines the survival and aging of cells. In cells that divide asymmetrically, such as Saccharomyces cerevisiae, aggregated proteins are retained by the mother cell. Yet, where and how aggregation occurs is not known. Recent work by Zhou and collaborators shows that the birth of protein aggregates, under specific stress conditions, requires active translation, and occurs mainly at the endoplasmic reticulum. Later, aggregates move to the mitochondrial surface through fis1-dependent associa- tion. During replicative aging, aggregate association with the mother-cell mitochondria contributes to the asym- metric segregation of aggregates, because mitochondria in the daughter cell do not carry aggregates. With increasing age of mother cells, aggregates lose their connection to the mitochondria, and segregation is less asymmetric. Relating these findings to other mechanisms of aggregate segregation in different organisms, we postulate that fusion between aggregates and their tethering to organelles such as the vacuole, nucleus, ER, or mitochondria are common principles that establish asymmetric segregation during stress resistance and aging

Fusion leads to effective segregation of damage during cell division: An analytical treatment

High levels of cellular damage are associated with impairment of cellular function and cell death. Partitioning the damage into a fraction of cells in the population improves population fitness and survival. We have previously shown that protein aggregates, resulting from misfolded, damaged proteins, fuse with each other leading to damage partitioning during cell division. Here, using an analytical treatment of aggregate fusion in dividing cells we present analytical expressions for two measures of damage partition: aggregate mass partition asymmetry between two dividing cells and standard deviation of total aggregate mass across the population. The scaling laws obtained demonstrate how damage partition may generally depend on characteristics of the cellular processes, facilitating better understanding of damage segregation in biological cells