[Frontiers in Bioscience 14, 1529-1557, January 1, 2009]

Key players in chromosome segregation in Caenorhabditis elegans

Risa Kitagawa

Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, U.S.A.

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Architecture of C. elegans kinetochore
3.1. Electron microscopic analysis of C. elegans kinetochore structure
3.2. Conserved kinetochore components in C. elegans
3.2.1. Proteins that establish the foundation for the kinetochore assembly
3.2.1.1. HCP-3/CeCENP-A
3.2.1.2. HCP-4/CeCENP-C
3.2.1.3. KNL-2
3.2.2. Outer kinetochore components that serve as core microtubule biding sites
3.2.2.1. KNL-1 protein
3.2.2.2. MIS-12 protein
3.2.2.3. KNL-3 protein
3.2.2.4. KBP-1 and KBP-2
3.2.2.5. NDC-80/CeHEC1
3.2.2.6. HIM-10/CeNUF-2
3.2.2.7. KBP-3 and KBP-4
3.2.3. Other proteins that localize to kinetochores
3.2.3.1. HCP-1/2/CeCENP-F
3.2.3.2. CLS-2/CeCLASP2
3.2.3.3. KLP-7/CeMCAK
3.2.3.4. LIS-1
3.2.3.5. KBP-5
3.2.3.6. MEL-28
3.3. Summary and perspectives
4. Protein complexes required for maintenance of mitotic chromosome organization
4.1. Role of the Condensin complex during chromosome segregation in C. elegans
4.2. Role of the Cohesin complex during chromosome segregation in C. elegans
4.3. Chromosomal passenger proteins in chromosome segregation
4.4. Summary and perspectives
5. Spindle assembly checkpoint in C. elegans
5.1. Spindle assembly checkpoint in embryonic cells
5.2. Spindle Assembly Checkpoint components
5.2.1. MDF-1/CeMAD-1 and MDF-2/CeMAD-2
5.2.2. SAN-1/CeMAD-3 5.2.3. BUB-1
5.2.4. BUB-3
5.2.5. RZZ (ROD-ZW10-ZWILCH) complex
5.3. Mutations that activate the spindle assembly checkpoint
5.4. Balance between the activity of the APC/C and that of the spindle assembly checkpoint
5.5. Summary and perspectives
6. Meiotic chromosome segregation in C. elegans
6.1. Architecture of the meiotic kinetochore in C. elegans
6.2. Localization of kinetochore components on bivalents
6.3. Role of cohesin and condensin in meiosis
6.4. Role of the spindle assembly checkpoint in meiosis
6.5. Summary and perspectives
7. Outstanding issues and future directions
7.1. Spindle assembly checkpoint activation in embryonic cells
7.2. Spindle assembly checkpoint function during postembryonic development
7.3. A reverse genetics approach to identify the synthetic genetic interactors with the spindle assembly checkpoint components.
7.4. Forward genetics approaches to studying the spindle assembly checkpoint in C. elegans
8. Acknowledgements
9. References

1. ABSTRACT

In contrast to many eukaryotic organisms in which kinetochores are assembled on localized centromeres of monocentric chromosomes, Caenorhabditis elegans has diffuse kinetochores, termed holo-kinetochores, which are assembled along the entire length of the mitotic chromosome. Despite this cytologically distinct chromosomal architecture, holo-kinetochores of C. elegans and kinetochores of other eukaryotes share structurally and functionally conserved properties. The amphitelic attachment of sister kinetochores to microtubules can be achieved by proper chromosomal organization, which relies on spatiotemporally orchestrated functions of conserved protein complexes such as the cohesin, condensin, and chromosomal passenger complexes during mitosis and meiosis in C. elegans. Moreover, the structure of spindle assembly checkpoint components and their safeguard function are also well conserved in C. elegans. Extensive efforts in the last few years to elucidate the molecular mechanisms of the C. elegans spindle assembly checkpoint have revealed its unique features. In this review, I will focus on the conservation and diversity of proteins that are required to maintain chromosome transmission fidelity during mitosis and meiosis in C. elegans.