Here, There, and Everywhere

Cytologists have long observed that individual eukaryotic species segregate their chromosomes in one of two apparently different ways. Monocentric chromosomes attach to microtubules at a particular region (the centromere) and move toward the pole during anaphase with the centromere leading. In contrast, holocentric chromosomes bind to microtubules along their entire length and move broadside to the pole from the metaphase plate. Holocentric chromosomes are scattered throughout the plant and animal kingdoms, and may be products of convergent evolution. Alternatively, the ancestral eukaryotic chromosome may have been holocentric, in which case the restriction of kinetic activity to a specialized region must have been an evolutionary event that occurred again and again. Perhaps because most laboratory organisms have monocentric chromosomes, holocentric species have been regarded with a mixture of curiosity and suspicion. These attitudes have begun to change precipitously due to three major factors: the development of the holocentric nematode worm Caenorhabditis elegans as a robust molecular genetic system, the availability of extensive genome sequences for both C. elegans and monocentric species, and the harnessing of RNA interference (RNAi) as an experimental technique (Fire et al., 1998). As these tools are enabling holocentric behavior to be studied at a molecular level, we can finally explore how a chromosome function as basic and essential as microtubule attachment has assumed such distinct evolutionary forms. Three studies published in this issue, combined with other recent results, strongly suggest that many components and mechanisms underlying kinetochore function are highly conserved between holocentric and monocentric chromosomes. Several C. elegans proteins have now been implicated in centromere function or kinetochore structure. The majority were first identified by virtue of their homology to components identified in monocentric organisms, including ZW10 (Starr et al., 1997), CENP-A (HCP-3) (Buchwitz et al., 1999), and now CENP-C (HCP-4) (see Moore and Roth, 2001; Oegema et al., 2001, in this issue), Bub1, and MCAK (Oegema et al., 2001). Homologs of chromosome “passenger proteins” similar to Aurora and INCENPs have also been recognized and shown to play roles in chromosome segregation (Schumacher et al., 1998; Kaitna et al., 2000; Oegema et al., 2001). In contrast, discovery of HCP-1 (and its partially redundant paralog HCP-2) originated with a monoclonal antibody that recognized the poleward face of mitotic chromosomes (Moore et al., 1999). HCP-1 and -2 are likely homologs of mammalian CENP-F, a kinetochore protein that is a component of the spindle assembly checkpoint (Rattner et al., 1993). Another player, HIM-10, was identified genetically through a partial loss-of-function allele that causes a nonlethal segregation defect (Hodgkin et al., 1979). In this issue, Howe et al. (2001) have now demonstrated a role in kinetochore function for HIM-10, which is homologous to Nuf2, originally identified as a spindle pole body–associated factor from budding yeast and recently shown to be centromeric in organisms from Schizosaccharomyces pombe to humans (Osborne et al., 1994; Wigge and Kilmartin, 2001). Each of these C. elegans centromere or kinetochore proteins thus shares similarity with centromere-associated factors from monocentric organisms. By studying these proteins in the context of holocentric chromosomes, work in this issue contributes to our understanding of the conserved, and probably most fundamental, properties of kinetochores. A summary of available information about kinetic assembly is presented in Fig. 1 (RNAi).