Sticky endings: separating telomeres.

Abstract

T he ends of eukaryotic chromosomes are capped by telomeres, which facilitate the replication of the ends of the DNA molecule. The telomeres of both homologous and nonhomologous chromosomes can easily self-associate, perhaps as a simple consequence of their structure—repeated arrays of a sequence at the ends of all of an organism's chromosomes. Indeed, the clustering of telomeres at one point in the nucleus, creating a so-called “bouquet” of chromosomes, has been noted in a variety of organisms ([1][1]). As discussed in a recent Perspective ([2][2]), these associations are sufficiently strong that the separation of telomeres presents a special problem for the meiotic and mitotic segregational systems. Evidence that cis- and trans-acting functions are required for the separation of telomeres at cell division has been recently obtained in Tetrahymena and Drosophila ( 3, 4 ). In this issue (page [1252][3]), Conrad et al . (5) report a gene ( NDJ1 ) that encodes a telomere-associated protein required for meiotic chromosome segregation in a third organism, the yeast Saccharomyces cerevisiae . This protein accumulates at the telomeres of chromosomes during meiotic prophase, and its absence results in high levels of failed meiotic chromosome segregation (meiotic nondisjunction). The failure of homolog separation at meiosis is observed whether or not the homologs have undergone genetic recombination. However, there is no effect of the absence of the Ndj1 protein on the segregation of telomere-less ring chromosomes, arguing that Ndj1 protein is not required for meiotic chromosome separation per se, but rather that the Ndj1 protein is essential to separate segregational partners that have telomeres. The Ndj1 protein is also required for the completion of homologous synapsis. Loss of the Ndj1 protein delays the formation of the axial elements of the synaptonemal complex, a structure that connects homologous meiotic chromosomes along their length, without affecting recombination. The mechanism by which the Ndj1 protein facilitates synapsis remains unclear, but the normal clustering of telomeres into a bouquet may create three-dimensional chromosome arrangements, such as interlocked bivalents, that would impede proper synapsis. An inability to dissolve telomere-telomere interactions, especially those between nonhomologous telomeres, might prevent the chromosomal movements required to resolve those problems and facilitate homologous alignments. Such a model nicely explains both the effects of Ndj1 deficiency on synapsis and segregation, and the rather curious lack of effect of this deficiency on ring chromosomes. Thus, even as cells have used telomeres to neatly solve the problem of replicating chromosomal ends, they have introduced difficulties for chromosomal movement because of the inherent stickiness of telomeres. Perhaps not surprisingly, cells have evolved ways to cope. 1. [↵][4]1. E. H. Blackburn, 2. C. W. Greider 1. A. F. Dernburg 2. et al. (1996) in Telomeres, eds E. H. Blackburn, C. W. Greider (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY), 295–338. 2. [↵][5]1. R. S. Hawley (1997) Science 275:1441. [OpenUrl][6][FREE Full Text][7] 3. 1. K. E. Kirk 2. et al. ibid. 1478. 4. 1. G. Cenci 2. et al. Genes Dev. 1997 11 863; [OpenUrl][8][Abstract/FREE Full Text][9] 1. M. N. Conrad 2. et al. , Science 276, 1252 (1997). 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