Cellular and Molecular Life Sciences

Maiato, Helder

doi: 10.1007/s00018-010-0320-zpmid: 20213271

Kops, Geert; Saurin, Adrian; Meraldi, Patrick

doi: 10.1007/s00018-010-0321-ypmid: 20232224

Genomic stability requires error-free chromosome segregation during mitosis. Chromosome congression to the spindle equator precedes chromosome segregation in anaphase and is a hallmark of metazoan mitosis. Here we review the current knowledge and concepts on the processes that underlie chromosome congression, including initial attachment to spindle microtubules, biorientation, and movements, from the perspective of the kinetochore.

McEwen, Bruce; Dong, Yimin

doi: 10.1007/s00018-010-0322-xpmid: 20336345

Kinetochore function is mediated through its interaction with microtubule plus ends embedded in the kinetochore outer plate. Here, we compare and evaluate current models for kinetochore microtubule attachment, beginning with a brief review of the molecular, biochemical, cellular, and structural studies upon which these models are based. The majority of these studies strongly support a model in which the kinetochore outer plate is a network of fibers that form multiple weak attachments to each microtubule, chiefly through the Ndc80 complex. Multiple weak attachments enable kinetochores to remain attached to microtubule plus ends that are continually growing and shrinking. It is unlikely that rings or “kinetochore fibrils” have a significant role in kinetochore microtubule attachment, but such entities could have a role in stabilizing attachment, modifying microtubule dynamics, and harnessing the energy released from microtubule disassembly. It is currently unclear whether kinetochores control and coordinate the dynamics of individual kinetochore microtubules.

Debec, Alain; Sullivan, William; Bettencourt-Dias, Monica

doi: 10.1007/s00018-010-0323-9pmid: 20300952

Centrioles are cylinders made of nine microtubule (MT) triplets present in many eukaryotes. Early studies, where centrosomes were seen at the poles of the mitotic spindle led to their coining as “the organ for cell division”. However, a variety of subsequent observational and functional studies showed that centrosomes might not always be essential for mitosis. Here we review the arguments in this debate. We describe the centriole structure and its distribution in the eukaryotic tree of life and clarify its role in the organization of the centrosome and cilia, with an historical perspective. An important aspect of the debate addressed in this review is how centrioles are inherited and the role of the spindle in this process. In particular, germline inheritance of centrosomes, such as their de novo formation in parthenogenetic species, poses many interesting questions. We finish by discussing the most likely functions of centrioles and laying out new research avenues.

Müller-Reichert, Thomas; Greenan, Garrett; O’Toole, Eileen; Srayko, Martin

doi: 10.1007/s00018-010-0324-8pmid: 20339898

The Caenorhabditis elegans one-cell embryo is a powerful system in which to study microtubule organization because this large cell assembles both meiotic and mitotic spindles within the same cytoplasm over the course of 1 h in a stereotypical manner. The fertilized oocyte assembles two consecutive acentrosomal meiotic spindles that function to reduce the replicated maternal diploid set of chromosomes to a single-copy haploid set. The resulting maternal DNA then unites with the paternal DNA to form a zygotic diploid complement, around which a centrosome-based mitotic spindle forms. The early C. elegans embryo is amenable to live-cell imaging and electron tomography, permitting a detailed structural comparison of the meiotic and mitotic modes of spindle assembly.

Wozniak, Richard; Burke, Brian; Doye, Valérie

doi: 10.1007/s00018-010-0325-7pmid: 20372967

The trafficking of macromolecules between the cytoplasm and the nucleus is controlled by the nuclear pore complexes (NPCs) and various transport factors that facilitate the movement of cargos through the NPCs and their accumulation in the target compartment. While their functions in transport are well established, an ever-growing number of observations have also linked components of the nuclear transport machinery to processes that control chromosome segregation during mitosis, including spindle assembly, kinetochore function, and the spindle assembly checkpoint. In this review, we will discuss this evolving area of study and emerging hypotheses that propose key roles for components of the nuclear transport apparatus in mitotic progression.

Civelekoglu-Scholey, Gul; Scholey, Jonathan

doi: 10.1007/s00018-010-0326-6pmid: 20221784

The mitotic spindle uses dynamic microtubules and mitotic motors to generate the pico-Newton scale forces that are needed to drive the mitotic movements that underlie chromosome capture, alignment and segregation. Here, we consider the biophysical and molecular basis of force-generation for chromosome movements in the spindle, and, with reference to the Drosophila embryo mitotic spindle, we briefly discuss how mathematical modeling can complement experimental analysis to illuminate the mechanisms of chromosome-to-pole motility during anaphase A and spindle elongation during anaphase B.

Maiato, Helder; Lince-Faria, Mariana

doi: 10.1007/s00018-010-0327-5pmid: 20306325

One of the most extraordinary events in the lifetime of a cell is the coordinated separation of sister chromatids during cell division. This is truly the essence of the entire mitotic process and the reason for the most profound morphological changes in cytoskeleton and nuclear organization that a cell may ever experience. It all occurs within a very short time window known as “anaphase”, as if the cell had spent the rest of its existence getting ready for this moment in an ultimate act of survival. And there is a good reason for this: no space for mistakes. Problems in the distribution of chromosomes during cell division have been correlated with aneuploidy, a common feature observed in cancers and several birth defects, and the main cause of spontaneous abortion in humans. In this paper, we critically review the mechanisms of anaphase chromosome motion that resisted the scrutiny of more than 100 years of research, as part of a tribute to the pioneering work of Miguel Mota.

Jeon, Young-Joo; Kim, Do-Hyung; Jung, Hyeyun; Chung, Sang; Chi, Seung-Wook; Cho, Sayeon; Lee, Sang; Park, Byoung; Park, Sung; Bae, Kwang-Hee

doi: 10.1007/s00018-010-0331-9pmid: 20237821

Hur, Shin-Kyoung; Park, Eun-Jung; Han, Ji-Eun; Kim, Yoon-Ah; Kim, Jong-Doo; Kang, Dongmin; Kwon, Jongbum

doi: 10.1007/s00018-010-0337-3pmid: 20237820

Although INO80 chromatin remodeling enzyme has been shown in yeast to play roles in non-transcriptional nuclear processes such as DNA replication, its cellular functions in higher eukaryotes have remained largely unexplored. Here, we provide evidence that human INO80 (hINO80) participates in both DNA replication and chromosome segregation during the normal cell division cycle. hINO80 binds to chromatin localizing at replication forks during the S-phase, and is required for efficient DNA synthesis and S-phase progression. Unexpectedly, hINO80 associates with spindle microtubule during mitosis, and its deficiency leads to defective microtubule assembly and abnormal chromosome segregation. Consistent with these results, hINO80 is critical for suppressing aneuploidy and structural chromosome abnormalities. This work therefore not only emphasizes the evolutionary importance of INO80 in DNA replication but also reveals a new role for this remodeler in chromosome segregation, both of which likely come into play in maintaining the genome integrity.